Patent application title: ALPHA-CONOTOXIN PEPTIDES
Inventors:
Maren Watkins (Salt Lake City, UT, US)
Baldomero M. Olivera (Salt Lake City, UT, US)
Baldomero M. Olivera (Salt Lake City, UT, US)
David R. Hillyard (Salt Lake City, UT, US)
J. Michael Mcintosh (Salt Lake City, UT, US)
J. Michael Mcintosh (Salt Lake City, UT, US)
Assignees:
The University of Utah Research Foundation
IPC8 Class: AC07K14435FI
USPC Class:
530322
Class name: Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof peptides of 3 to 100 amino acid residues peptides containing saccharide radicals, e.g., bleomycins, etc.
Publication date: 2014-11-27
Patent application number: 20140350218
Abstract:
The invention relates to relatively short peptides (termed
α-conotoxins herein), about 10-30 residues in length, which are
naturally available in minute amounts in the venom of the cone snails or
analogous to the naturally available peptides, and which preferably
include two disulfide bonds.Claims:
1. A substantially pure α-conotoxin peptide selected from the group
consisting of:
TABLE-US-00139
(SEQ ID NO: 4)
Asp-Xaa1-Cys-Cys-Ser-Asp-Ser-Arg-Cys-
Gly-Xaa2-Asn-Cys-Leu;
(SEQ ID NO: 5)
Ala-Cys-Cys-Ser-Asp-Arg-Arg-Cys-Arg-
Xaa3-Arg-Cys;
(SEQ ID NO: 6)
Phe-Thr-Cys-Cys-Arg-Arg-Gly-Thr-Cys-
Ser-Gln-His-Cys;
(SEQ ID NO: 7)
Asp-Xaa4-Cys-Cys-Arg-Arg-His-Ala-Cys-
Thr-Leu-Ile-Cys;
(SEQ ID NO: 8)
Asp-Xaa4-Cys-Cys-Arg-Xaa5-Xaa5-Cys-Thr-
Leu-Ile-Cys;
(SEQ ID NO: 10)
Gly-Gly-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-
Ala-Xaa3-Arg-Cys;
(SEQ ID NO: 11)
Ile-Ala-Xaa3-Asp-Ile-Cys-Cys-Ser-Xaa1-
Xaa5-Asp-Cys-Asn-His-Xaa2-Cys-Val;
and
(SEQ ID NO: 12)
Gly-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Xaa2-
His-Gln-Cys,
wherein Xaa1 is Glu or γ-carboxy-Glu (Gla); Xaa2 is Lys, N-methyl-Lys, N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa3 is Trp (D or L), halo-Trp or neo-Trp; Xaa4 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr; and Xaa5 is Pro or hydroxy-Pro; and the C-terminus contains a carboxyl or amide group, or derivatives thereof.
2. The substantially pure α-conotoxin peptide of claim 1, which is modified to contain an O-glycan, an S-glycan or an N-glycan.
3. A substantially pure α-conotoxin peptide having the generic formula II: Xaa1-Xaa2-Xaa3-Xaa4-Cys-Cys-Xaa5-Xaa6-Xaa.s- ub.7-Xaa8-Cys-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-X- aa14-Cys-Xaa15-Xaa16-Xaa17 (SEQ ID NO:2), wherein Xaa1 is des-Xaa1, Asp, Glu or γ-carboxy-Glu (Gla); Xaa2 is des-Xaa2, Gln, Ala, Asp, Glu, Gla; Xaa3 is des-Xaa3, Gly, Ala, Asp, Glu, Gla, Pro or hydroxy-Pro; Xaa4 is des-Xaa4, Gly, Glu, Gla, Gln, Asp, Asn, Pro or hydroxy-Pro; Xaa5 is Ser, Thr, Gly, Glu, Gla, Asn, Trp (D or L), neo-Trp, halo-Trp, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa6 is Asp, Asn, His, halo-His, Thr, Ser, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa7 is Pro or hydroxy-Pro; Xaa8 is Ala, Ser, Thr, Asp, Val, Ile, Pro, hydroxy-Pro, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa9 is Gly, Ile, Leu, Val, Ala, Thr, Ser, Pro, hydroxy-Pro, Phe, Trp (D or L), neo-Trp, halo-Trp, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid or any unnatural aromatic amino acid; Xaa10 is Ala, Asn, Phe, Pro, hydroxy-Pro, Glu, Gla, Gln, His, halo-His, Val, Ser, Thr, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa11 is Thr, Ser, His, halo-His, Leu, Ile, Val, Asn, Met, Pro, hydroxy-Pro, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa12 is Asn, Pro, hydroxy-Pro, Gln, Ser, Thr, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys N,N,N-trimethyl-Lys, any unnatural basic amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa13 is des-Xaa13, Gly, Thr, Ser, Pro, hydroxy-Pro, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa14 is des-Xaa14, Ile, Val, Asp, Leu, Phe, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; and Xaa15 is des-Xaa15, Gly, Ala, Met, Ser, Thr, Trp (D or L), neo-Trp, halo-Trp, any unnatural aromatic amino acid, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa16 is des-Xaa16, Trp (D or L), neo-Trp, halo-Trp, any unnatural aromatic amino acid, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa17 is des-Xaa17, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; and the C-terminus contains a free carboxyl group or an amide group.
4. A substantially pure α-conotoxin peptide of generic formula II of claim 3 selected from the group consisting of: TABLE-US-00140 (SEQ ID NO: 13) Cys-Cys-Ser-Asp-Xaa5-Ala-Cys-Xaa2-Gln-Thr-Xaa5-Gly-Cys-Arg; (SEQ ID NO: 14) Cys-Cys-Xaa1-Asn-Xaa5-Ala-Cys-Arg-His-Thr-Gln-Gly-Cys; (SEQ ID NO: 15) Gly-Cys-Cys-Xaa3-His-Xaa5-Ala-Cys-Gly-Arg-His-Xaa4-Cys; (SEQ ID NO: 16) Ala-Xaa5-Cys-Cys-Asn-Asn-Xaa5-Ala-Cys-Val-Xaa2-His-Arg-Cys; (SEQ ID NO: 17) Ala-Xaa5-Gly-Cys-Cys-Asn-Asn-Xaa5-Ala-Cys-Val-Xaa2-His-Arg-- Cys; (SEQ ID NO: 18) Xaa5-Xaa5-Cys-Cys-Asn-Asn-Xaa5-Ala-Cys-Val-Xaa2-His-Ar- g-Cys; (SEQ ID NO: 19) Asp-Xaa1-Asn-Cys-Cys-Xaa3-Asn-Xaa5-Ser-Cys-Xaa5-Arg-Xa- a5-Arg-Cys-Thr; (SEQ ID NO: 20) Gly-Cys-Cys-Ser-Thr-Xaa5-Xaa5-Cys-Ala-Val-Leu-Xaa4-Cys; (SEQ ID NO: 21) Gly-Cys-Cys-Gly-Asn-Xaa5-Asp-Cys-Thr-Ser-His-Ser-Cys; (SEQ ID NO: 42) Gly-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ala-His-Asn-Asn-Xaa5-Asp-- Cys-Arg; (SEQ ID NO: 154) Gly-Cys-Cys-Xaa4-Asn-Xaa5-Val-Cys-Xaa2-Xaa2-Xaa4-- Xaa4-Cys-Xaa3-Xaa2; (SEQ ID NO: 155) Xaa6-Xaa1-Xaa5-Gly-Cys-Cys-Arg-His-Xaa5-Ala-Cys-Gly-Xa- a2-Asn-Arg-Cys; (SEQ ID NO: 156) Cys-Cys-Ala-Asp-Xaa5-Asp-Cys-Arg-Phe-Arg-Xaa5-Gly-Cys; (SEQ ID NO: 157) Gly-Cys-Cys-Xaa4-Asn-Xaa5-Ser-Cys-Xaa3-Xaa5-Xaa2-- Thr-Xaa4-Cys-Ser-Xaa3- Xaa2; (SEQ ID NO: 158) Cys-Cys-Ser-Asn-Xaa5-Thr-Cys-Xaa2-Xaa1-Thr-Xaa4-Gly-Cy- s; (SEQ ID NO: 159) Cys-Cys-Ala-Asn-Xaa5-Ile-Cys-Xaa2-Asn-Thr-Xaa5-Gly-Cys; (SEQ ID NO: 160) Cys-Cys-Asn-Asn-Xaa5-Thr-Cys-Xaa2-Xaa1-Thr-Xaa4-Gly-Cy- s; (SEQ ID NO: 161) Cys-Cys-Ser-Asn-Xaa5-Val-Cys-Xaa2-Xaa1-Thr-Xaa4-Gly-Cy- s; (SEQ ID NO: 162) Gly-Gly-Cys-Cys-Ser-Xaa4-Xaa5-Xaa5-Cys-Ile-Ala-Ser-Asn-Xaa.- sub.5-Xaa2-Cys-Gly; (SEQ ID NO: 163) Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Ser-Ala-Met-Ser-Xaa5-Ile-Cys; (SEQ ID NO: 164) Gly-Cys-Cys-Xaa2-Asn-Xaa5-Xaa4-Cys-Gly-Ala-Ser-Xaa2-Th- r-Xaa4-Cys; (SEQ ID NO: 165) Gly-Cys-Cys-Ser-Xaa4-Xaa5-Xaa5-Cys-Phe-Ala-Thr-Asn-Xaa5-Asp-Cys; (SEQ ID NO: 166) Gly-Gly-Cys-Cys-Ser-Xaa4-Xaa5-Xaa5-Cys-Ile-Ala-Asn-Asn-Xaa.- sub.5-Leu-Cys-Ala; (SEQ ID NO: 167) Gly-Gly-Cys-Cys-Ser-Xaa4-Xaa5-Xaa5-Cys-Ile-Ala-Asn-Asn-Xaa.- sub.5-Phe-Cys-Ala; (SEQ ID NO: 168) Asp-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ser-Gln-Asn-Asn-Xaa5-Asp-- Cys-Met; and (SEQ ID NO: 169) Asp-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ala-His-Asn-Asn-Xaa5-Asp-- Cys-Arg,
wherein Xaa1 is Glu or γ-carboxy-Glu (Gla); Xaa2 is Lys, N-methyl-Lys, N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa3 is Trp (D or L), halo-Trp or neo-Trp; Xaa4 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr; and Xaa5 is Pro or hydroxy-Pro; and the C-terminus contains a carboxyl or amide group, or derivatives thereof.
5. The substantially pure α-conotoxin peptide of claim 3, which is modified to contain an O-glycan, an S-glycan or an N-glycan.
6. The substantially pure α-conotoxin peptide of claim 4 which is modified to contain an O-glycan, an S-glycan or an N-glycan.
7. A substantially pure α-conotoxin peptide selected from the group consisting of: TABLE-US-00141 (SEQ ID NO: 22) Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa1-His-Ser-Asn-Met-Cy- s; (SEQ ID NO: 23) Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-Arg-Gln-Asn-Asn-Ala-Xaa1-Xaa.su- b.4-Cys-Arg; (SEQ ID NO: 24) Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-- Xaa1-Ile-Cys- Arg; (SEQ ID NO: 25) Xaa5-Xaa1-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa.- sub.5-Xaa1-Ile- Cys-Arg; (SEQ ID NO: 26) Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-- Xaa1-Ile-Cys- Asp; (SEQ ID NO: 27) Xaa5-Arg-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-- Xaa1-Ile-Cys- Arg; (SEQ ID NO: 28) Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-- Gly-Ile-Cys- Arg; (SEQ ID NO: 29) Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-- Xaa1-Thr- Cys-Arg; (SEQ ID NO: 30) Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-- Xaa1-Val- Cys-Arg; (SEQ ID NO: 31) Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Ile-Asp-His-Xaa5-- Xaa1-Ile-Cys- Arg; (SEQ ID NO: 32) Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-- Xaa1-Ile-Cys- Arg-Arg-Arg-Arg; (SEQ ID NO: 33) Gly-Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Val-Asn-His-Xaa5-Xaa.su- b.1-Leu-Cys; (SEQ ID NO: 35) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-- Ile-Cys; (SEQ ID NO: 36) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Xaa2-Thr-Gln-Xaa1-- Xaa5-Cys-Arg- Xaa1-Ser; (SEQ ID NO: 37) Xaa5-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Asn-Asn-Xaa5-Xaa.- sub.1-Phe-Cys- Arg-Gln; (SEQ ID NO: 38) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Asn-Asn-Xaa5-Xaa1-- Phe-Cys-Arg- Gln; (SEQ ID NO: 39) Gly-Cys-Cys-Ser-His-Xaa5-Xaa5-Cys-Ala-Met-Asn-Asn-Xaa5-Asp-- Xaa4-Cys; (SEQ ID NO: 40) Gly-Cys-Cys-Ser-His-Xaa5-Xaa5-Cys-Phe-Leu-Asn-Asn-Xaa5-Asp-- Xaa4-Cys; (SEQ ID NO: 41) Gly-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ile-Ala-Xaa2-Asn-Xaa5-His-Met-Cys-Gly; (SEQ ID NO: 43) Gly-Cys-Cys-Ser-Asn-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Xaa5-His-Val-Cy- s-Arg- Gln; (SEQ ID NO: 44) Gly-Cys-Cys-Ser-Arg-Xaa5-Ala-Cys-Ile-Ala-Asn-Asn-Xaa5-Asp-Leu-Cy- s; (SEQ ID NO: 45) Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Val-Xaa1-His-Xaa5-Xaa.- sub.1-Leu-Cys- Arg-Arg-Arg-Arg; (SEQ ID NO: 46) Gly-Gly-Cys-Cys-Ser-Phe-Xaa5-Ala-Cys-Arg-Xaa2-Xaa5-Arg-Xaa.- sub.5-Xaa1-Met- Cys-Gly; (SEQ ID NO: 47) Xaa5-Xaa1-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Ser-Ser-His-Xaa.- sub.5-Xaa1-Leu- Cys-Gly; (SEQ ID NO: 48) Xaa5-Gln-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Val-Gly-His-Xaa5-- Xaa1-Leu- Cys-Gly; (SEQ ID NO: 49) Xaa6-Val-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Val-Gly-His-Xaa5-- Xaa1-Ile-Cys- Gly; (SEQ ID NO: 50) Gly-Cys-Cys-Ser-Arg-Xaa5-Xaa5-Cys-Ile-Ala-Asn-Asn-Xaa5-Asp-- Leu-Cys; (SEQ ID NO: 51) Xaa5-Gln-Cys-Cys-Ser-His-Leu-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa.su- b.1-Ile-Cys- Arg; (SEQ ID NO: 52) Gly-Cys-Cys-Ser-Xaa4-Phe-Asp-Cys-Arg-Met-Met-Phe-Xaa5-Xaa1-- Met-Cys- Gly-Xaa3-Arg; (SEQ ID NO: 53) Gly-Gly-Cys-Cys-Ser-Phe-Ala-Ala-Cys-Arg-Xaa2-Xaa4-Arg-Xaa5-- Xaa1-Met- Cys-Gly; (SEQ ID NO: 54) Gly-Gly-Cys-Cys-Phe-His-Xaa5-Val-Cys-Xaa4-Ile-Asn-Leu-Leu-Xaa.su- b.1-Met-Cys- Arg-Gln-Arg; (SEQ ID NO: 55) Ser-Ala-Thr-Cys-Cys-Asn-Xaa4-Xaa5-Xaa5-Cys-Xaa4-Xaa.su- b.1-Thr-Xaa4-Xaa5- Xaa1-Ser-Cys-Leu; (SEQ ID NO: 56) Ala-Cys-Cys-Ala-Xaa4-Xaa5-Xaa5-Cys-Phe-Xaa1-Ala-Xaa.su- b.4-Xaa5-Xaa1-Arg-Cys- Leu; (SEQ ID NO: 57) Asn-Ala-Xaa1-Cys-Cys-Xaa4-Xaa4-Xaa5-Xaa5-Cys-Xaa.- sub.4-Xaa1-Ala-Xaa4-Xaa5- Xaa1-Ile-Cys-Leu; (SEQ ID NO: 170) Xaa1-Cys-Cys-Thr-Asn-Xaa5-Val-Cys-His-Ala-Xaa1-His-Gln-Xaa.- sub.1-Leu-Cys- Ala-Arg-Arg-Arg; (SEQ ID NO: 171) Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa1-His-Ser-Asn-Leu-Cy- s; (SEQ ID NO: 172) Xaa1-Cys-Cys-Thr-Asn-Xaa5-Val-Cys-His-Val-Xaa1-His-Gln-Xaa.- sub.1-Leu-Cys- Ala-Arg-Arg-Arg; (SEQ ID NO: 173) Xaa6-Xaa1-Cys-Cys-Ser-Xaa4-Xaa5-Ala-Cys-Asn-Leu-Asp-Hi- s-Xaa5-Xaa1-Leu- Cys; (SEQ ID NO: 174) Xaa5-Xaa1-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Ser-Thr-His-Xaa.- sub.5-Xaa1-Leu- Cys-Gly; (SEQ ID NO: 175) Leu-Asn-Cys-Cys-Met-Ile-Xaa5-Xaa5-Cys-Xaa3-Xaa2-Xaa.su- b.2-Xaa4-Gly-Asp-Arg- Cys-Ser-Xaa1-Val-Arg; (SEQ ID NO: 176) Ala-Phe-Gly-Cys-Cys-Asp-Leu-Ile-Xaa5-Cys-Leu-Xaa1-Arg-Xaa4-- Gly-Asn-Arg- Cys-Asn-Xaa1-Val-His; (SEQ ID NO: 177) Leu-Gly-Cys-Cys-Asn-Val-Thr-Xaa5-Cys-Xaa3-Xaa1-Xaa2-Xa- a4-Gly-Asp-Xaa2- Cys-Asn-Xaa1-Val-Arg; (SEQ ID NO: 179) Leu-Asn-Cys-Cys-Ser-Ile-Xaa5-Gly-Cys-Xaa3-Asn-Xaa1-Xaa4-Xaa2-Asp-Arg- Cys-Ser-Xaa2-Val-Arg; (SEQ ID NO: 180) Gly-Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Xaa4-Phe-Asn-Asn-Xaa5-- Gln-Met-Cys- Arg; (SEQ ID NO: 181) Gly-Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Asn-Leu-Asn-Asn-Xaa5-Gln-Me- t-Cys- Arg;
(SEQ ID NO: 182) Gly-Cys-Cys-Ser-His-Xaa5-Xaa5-Cys-Xaa4-Ala-Asn-Asn-Gln-Ala-- Xaa4-Cys-Asn; (SEQ ID NO: 183) Gly-Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Val-Thr-His-Xaa5-Xaa.su- b.1-Leu-Cys; (SEQ ID NO: 184) Gly-Gly-Cys-Cys-Ser-Xaa4-Xaa5-Ala-Cys-Ser-Val-Xaa1-His-Gln-- Asp-Leu-Cys- Asp; (SEQ ID NO: 185) Val-Ser-Cys-Cys-Val-Val-Arg-Xaa5-Cys-Xaa3-Ile-Arg-Xaa4-Gln-- Xaa1-Xaa1- Cys-Leu-Xaa1-Ala-Asp-Xaa5-Arg-Thr-Leu; (SEQ ID NO: 186) Xaa6-Asn-Cys-Cys-Ser-Ile-Xaa5-Gly-Cys-Xaa3-Xaa1-Xaa.su- b.2-Xaa4-Gly-Asp-Xaa2- Cys-Ser-Xaa1-Val-Arg; (SEQ ID NO: 187) Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa1-His-Xaa5-Asn-- Ala-Cys; (SEQ ID NO: 188) Gly-Cys-Cys-Ser-Asn-Xaa5-Ile-Cys-Xaa4-Phe-Asn-Asn-Xaa5-Arg-- Ile-Cys-Arg; (SEQ ID NO: 189) Xaa1-Cys-Cys-Ser-Gln-Xaa5-Xaa5-Cys-Arg-Xaa3-Xaa2-- His-Xaa5-Xaa1-Leu-Cys- Ser; (SEQ ID NO: 190) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Gln-His-Ile-Cys; (SEQ ID NO: 191) Gly-Cys-Cys-Ala-Val-Xaa5-Ser-Cys-Arg-Leu-Arg-Asn-Xaa5-Asp-Leu-Cy- s-Gly- Gly; (SEQ ID NO: 192) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asn-Asn-Xaa5-His-Ile-Cy- s; (SEQ ID NO: 193) Thr-Xaa5-Xaa1-Xaa1-Cys-Cys-Xaa5-Asn-Xaa5-Xaa5-Cys-Phe-Ala-Thr-Asn-Ser- Asp-Ile-Cys-Gly; (SEQ ID NO: 194) Asp-Ala-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Gly-Xaa2-His-Gln-Asp-Le- u-Cys; (SEQ ID NO: 195) Xaa1-Asp-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Val-Gly-His-Gln-Asp-Le- u-Cys; (SEQ ID NO: 196) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Ser-Asn-Ala-His-Ile-Cys; (SEQ ID NO: 197) Xaa1-Asp-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Val-Gly-His-Gln-Asp-Me- t-Cys; (SEQ ID NO: 198) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Xaa5-His-Ile-Cy- s; (SEQ ID NO: 199) Gly-Cys-Cys-Gly-Asn-Xaa5-Ser-Cys-Ser-Ile-His-Ile-Xaa5-Xaa4-- Val-Cys-Asn; (SEQ ID NO: 200) Thr-Asp-Ser-Xaa1-Xaa1-Cys-Cys-Leu-Asp-Ser-Arg-Cys-Ala-Gly-Gln-Hi- s-Gln- Asp-Leu-Cys-Gly; (SEQ ID NO: 201) Gly-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Xaa4-Ala-Asn-Asn-Gln-Ala-- Xaa4-Cys- Asn; (SEQ ID NO: 202) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Val-Asn-Asn-Xaa5-Asp-Ile-Cy- s; (SEQ ID NO: 203) Gly-Xaa2-Cys-Cys-Ile-Asn-Asp-Ala-Cys-Arg-Ser-Xaa2-His-Xaa5-- Gln-Xaa4-Cys- Ser; (SEQ ID NO: 204) Gly-Cys-Cys-Xaa4-Asn-Ile-Ala-Cys-Arg-Ile-Asn-Asn-Xaa5-Arg-Xaa.su- b.4-Cys-Arg; (SEQ ID NO: 205) Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Arg-Phe-Asn-Xaa4-Xaa5-Xaa.- sub.2-Xaa4-Cys- Gly; (SEQ ID NO: 206) Asp-Xaa1-Cys-Cys-Ala-Ser-Xaa5-Xaa5-Cys-Arg-Leu-Asn-Asn-Xaa.- sub.5-Xaa4-Val- Cys-His; (SEQ ID NO: 207) Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-Xaa3-Gln-Asn-Asn-Ala-Xaa1-- Xaa4-Cys- Arg-Xaa1-Ser; (SEQ ID NO: 208) Gly-Cys-Cys-Ser-His-Xaa5-Xaa5-Cys-Ala-Gln-Asn-Asn-Gln-Asp-Xaa.su- b.4-Cys; (SEQ ID NO: 209) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Asn-Asn-Arg-Xaa1-Xaa.su- b.4-Cys-Arg- Xaa1-Ser; (SEQ ID NO: 210) Asp-Xaa5-Cys-Cys-Ser-Xaa4-Xaa5-Asp-Cys-Gly-Ala-Asn-His-Xaa.- sub.5-Xaa1-Ile- Cys-Gly; (SEQ ID NO: 211) Xaa1-Cys-Cys-Ser-Gln-Xaa5-Xaa5-Cys-Arg-Xaa3-Xaa2-- His-Xaa5-Xaa1-Leu-Cys- Ser; (SEQ ID NO: 212) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Xaa5-His-Ile-Cy- s; (SEQ ID NO: 213) Gly-Cys-Cys-Ser-Asp-Xaa5-Ser-Cys-Asn-Val-Asn-Asn-Xaa5-Asp-Xaa.su- b.4-Cys; (SEQ ID NO: 214) Xaa1-Xaa1-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Val-Gly-His-Gln-- Asp-Met-Cys- Arg; (SEQ ID NO: 215) Gly-Gly-Cys-Cys-Ser-Asn-Xaa5-Ala-Cys-Leu-Val-Asn-His-Leu-Xaa1-Me- t-Cys; (SEQ ID NO: 216) Arg-Asp-Xaa5-Cys-Cys-Phe-Asn-Xaa5-Ala-Cys-Asn-Val-Asn-Asn-Xaa.su- b.5-Gln-Ile- Cys; (SEQ ID NO: 217) Cys-Cys-Ser-Asp-Xaa5-Ser-Cys-Xaa3-Arg-Leu-His-Ser-Leu-Ala-Cys-Th- r-Gly- Ile-Val-Asn-Arg; (SEQ ID NO: 218) Cys-Cys-Thr-Asn-Xaa5-Ala-Cys-Leu-Val-Asn-Asn-Ile-Arg-Phe-Cys-Gly; (SEQ ID NO: 219) Asp-Xaa1-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-His-Gly-Asn-Asn-Arg-Asp-Hi- s-Cys- Ala; (SEQ ID NO: 220) Asp-Cys-Cys-Ser-His-Xaa5-Leu-Cys-Arg-Leu-Phe-Val-Xaa5-Gly-Leu-Cy- s-Ile; (SEQ ID NO: 221) Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Xaa2-Val-Arg-Xaa4-Xaa5-Asp-Leu-Cys-Arg; (SEQ ID NO: 222) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asn-Asn-Xaa5-His-Ile-Cy- s; (SEQ ID NO: 223) Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Xaa2-Val-Arg-Xaa4-Ser-Asp-- Met-Cys; (SEQ ID NO: 224) Gly-Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Xaa2-Val-His-Phe-Xaa5-- His-Ser-Cys; (SEQ ID NO: 225) Val-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Val-Asp-His-Xaa5-Xaa1-- Leu-Cys-Arg- Arg-Arg-Arg; (SEQ ID NO: 226) Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Asn-Leu-Ser-Asn-Xaa5-Gln-Ile-Cy- s-Arg; (SEQ ID NO: 227) Xaa6-Xaa1-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa.- sub.5-Xaa1-Ile- Cys-Arg; (SEQ ID NO: 228) Gly-Cys-Cys-Ser-Asn-Xaa5-Ala-Cys-Leu-Val-Asn-His-Ile-Arg-Phe-Cys-Gly; (SEQ ID NO: 229) Asp-Cys-Cys-Asp-Asp-Xaa5-Ala-Cys-Thr-Val-Asn-Asn-Xaa5-Gly-Leu-Cy- s-Thr; and (SEQ ID NO: 230) Gly-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ile-Ala-Xaa2-Asn-Xaa5-His-Met-Cys-Gly- Gly-Arg-Arg,
wherein Xaa1 is Glu or γ-carboxy-Glu (Gla); Xaa2 is Lys, N-methyl-Lys, N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa3 is Trp (D or L), halo-Trp or neo-Trp; Xaa4 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr; and Xaa5 is Pro or hydroxy-Pro; Xaa6 is Gln or pyro-Glu; and the C-terminus contains a carboxyl or amide group, or derivatives thereof.
8. The substantially pure α-conotoxin peptide of claim 7, which is modified to contain an O-glycan, an S-glycan or an N-glycan.
9. A substantially pure α-conotoxin peptide selected from the group consisting of: TABLE-US-00142 (SEQ ID NO: 231) Cys-Cys-Thr-Ile-Xaa5-Ser-Cys-Xaa4-Xaa1- Xaa2-Xaa2-Xaa2-Ile-Xaa2-Ala-Cys-Val-Phe and (SEQ ID NO: 232) Gly-Cys-Cys-Gly-Asn-Xaa5-Ala-Cys-Ser- Gly-Ser-Ser-Xaa2-Asp-Ala-Xaa5-Ser-Cys,
wherein Xaa1 is Glu or γ-carboxy-Glu (Gla); Xaa2 is Lys, N-methyl-Lys, N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa4 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr; and Xaa5 is Pro or hydroxy-Pro; and the C-terminus contains a carboxyl or amide group, or derivatives thereof.
10. The substantially pure α-conotoxin peptide of claim 9, which is modified to contain an O-glycan, an S-glycan or an N-glycan.
Description:
CROSS-REFERENCE TO RELATED APPLICATION
[0001] The present application is a division of U.S. patent application Ser. No. 13/367,839 filed 7 Feb. 2012, which in turn is a division of U.S. patent application Ser. No. 13/042,832 filed 8 Mar. 2011, now U.S. Pat. No. 8,110,549, which in turn is a division of U.S. patent application Ser. No. 12/706,911 filed 17 Feb. 2010, now U.S. Pat. No. 7,902,153, which in turn is a division of U.S. patent application Ser. No. 11/869,480 filed 9 Oct. 2007, now U.S. Pat. No. 7,666,840, which in turn is a division of U.S. patent application Ser. No. 10/895,372 filed 21 Jul. 2004, now U.S. Pat. No. 7,279,549, which in turn is a division of U.S. patent application Ser. No. 09/493,795 filed 28 Jan. 2000, now U.S. Pat. No. 6,797,808. U.S. patent application Ser. No. 09/493,795 is related to and claims priority under 35 U.S.C. §119(e) to U.S. provisional patent application Ser. No. 60/118,381, filed 29 Jan. 1999. Each application is incorporated herein by reference.
SEQUENCE SUBMISSION
[0003] The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is entitled 2323254SequenceListing.txt, was created on 5 Jun. 2013 and is 253 kb in size. The information in the electronic format of the Sequence Listing is part of the present application and is incorporated herein by reference in its entirety.
BACKGROUND OF THE INVENTION
[0004] The invention relates to relatively short peptides (termed α-conotoxins herein), about 10-30 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include two disulfide bonds.
[0005] The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated by reference, and for convenience are referenced in the following text by author and date and are listed alphabetically by author in the appended bibliography.
[0006] The predatory cone snails (Conus) have developed a unique biological strategy. Their venom contains relatively small peptides that are targeted to various neuromuscular receptors and may be equivalent in their pharmacological diversity to the alkaloids of plants or secondary metabolites of microorganisms. Many of these peptides are among the smallest nucleic acid-encoded translation products having defined conformations, and as such, they are somewhat unusual. Peptides in this size range normally equilibrate among many conformations. Proteins having a fixed conformation are generally much larger.
[0007] The cone snails that produce these peptides are a large genus of venomous gastropods comprising approximately 500 species. All cone snail species are predators that inject venom to capture prey, and the spectrum of animals that the genus as a whole can envenomate is broad. A wide variety of hunting strategies are used; however, every Conus species uses fundamentally the same basic pattern of envenomation.
[0008] Several peptides isolated from Conus venoms have been characterized. These include the α-, μ- and ω-conotoxins which target nicotinic acetylcholine receptors, muscle sodium channels, and neuronal calcium channels, respectively (Olivera et al., 1985). Conopressins, which are vasopressin analogs, have also been identified (Cruz et al. 1987). In addition, peptides named conantokins have been isolated from Conus geographus and Conus tulipa (Mena et al., 1990; Haack et al., 1990).
[0009] The α-conotoxins are small peptides highly specific for neuromuscular junction nicotinic acetylcholine receptors (Gray et al., 1981; Marshall and Harvey, 1990; Blount et al., 1992; Jacobsen et al., 1997) or highly specific for neuronal nicotinic acetylcholine receptors (Fainzilber et al., 1994; Johnson et al., 1995; Cartier et al., 1996; Luo et al., 1998). The α-conotoxins with specificity for neuromuscular junction nicotinic acetylcholine receptors are used as neuromuscular blocking agents for use in conjunction with surgery, as disclosed in U.S. patent application Ser. No. 09/488,799, filed 21 Jan. 2000, incorporated by reference herein. Additional α-conotoxins and uses for them have been described in U.S. Pat. No. 4,447,356 (Olivera et al., 1984); U.S. Pat. Nos. 5,432,155; 5,514,774, each incorporated herein by reference.
[0010] Additional uses for α-conotoxins are described in U.S. Ser. No. 09/219,446, filed 22 Dec. 1998, incorporated herein by reference. In this application, α-conotoxins with specificity for neuronal nicotinic acetylcholine receptors are used for treating disorders regulated at neuronal nicotinic acetylcholine receptors. Such disorders include, but are not limited to, cardiovascular disorders, gastric motility disorders, urinary incontinence, nicotine addiction, mood disorders (such as bipolar disorder, unipolar depression, dysthymia and seasonal effective disorder) and small cell lung carcinoma, as well as the localization of small cell lung carcinoma.
[0011] It is desired to provide additional α-conotoxin peptides having uses as described herein.
SUMMARY OF THE INVENTION
[0012] The invention relates to relatively short peptides (termed α-conotoxins herein), about 10-30 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include two disulfide bonds.
[0013] More specifically, the present invention is directed to α-conotoxin peptides having the general formula I:
[0014] Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Cys-Cys-Xaa6- -Xaa7-Xaa8-Xaa9-Cys-Xaa10-Xaa11-Xaa12-Cys-Xa- a13 (SEQ ID NO1:), wherein Xaa1 is des-Xaa1, Ile, Leu or Val; Xaa2 is des-Xaa2, Ala or Gly; Xaa3 is des-Xaa3, Gly, Trp (D or L), neo-Trp, halo-Trp or any unnatural aromatic amino acid; Xaa4 is des-Xaa4, Asp, Phe, Gly, Ala, Glu,γ-carboxy-Glu (Gla) or any unnatural aromatic amino acid; Xaa5 is Glu, Gla, Asp, Ala, Thr, Ser, Gly, Ile, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa6 is Ser, Thr, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa7 is Asp, Glu, Gla, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa8 is Ser, Thr, Asn, Ala, Gly, Arg, Lys, ornithine, homoarginine, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid, His, halo-His, Pro or hydroxy-Pro; Xaa9 is Thr, Ser, Ala, Asp, Asn, Pro, hydroxy-Pro, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa10 is Gly, Ser, Thr, Ala, Asn, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa11 is Gln, Leu, His, halo-His, Trp (D or L), halo-Trp, neo-Trp, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid or any unnatural aromatic amino acid; Xaa12 is Asn, His, halo-His, Ile, Leu, Val, Gln, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa13 is des-Xaa13, Val, Ile, Leu, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid. The C-terminus may contain a free carboxyl group or an amide group. The halo is chlorine, bromine or iodine, preferably iodine for Tyr and His and preferably bromine for Trp. The Cys residues may be in D or L configuration and may optionally be substituted with homocysteine (D or L). The Tyr residues may be substituted with the 3-hydroxyl or 2-hydroxyl isomers and corresponding O-sulpho- and O-phospho-derivatives. The acidic amino acid residues may be substituted with any synthetic acidic bioisoteric amino acid surrogate, e.g., tetrazolyl derivatives of Gly and Ala.
[0015] More specifically, the present invention is directed to α-conotoxin peptides having the general formula II:
[0016] Xaa1-Xaa2-Xaa3-Xaa4-Cys-Cys-Xaa5-Xaa6- -Xaa7-Xaa8-Cys-Xaa9-Xaa10-Xaa11-Xaa12-Xaa.su- b.13-Xaa14-Cys-Xaa15-Xaa16-Xaa17 (SEQ ID NO:2), wherein Xaa1 is des-Xaa1, Asp, Glu or γ-carboxy-Glu (Gla); Xaa2 is des-Xaa2, Gln, Ala, Asp, Glu, Gla; Xaa3 is des-Xaa3, Gly, Ala, Asp, Glu, Gla, Pro or hydroxy-Pro; Xaa4 is des-Xaa4, Gly, Glu, Gla, Gln, Asp, Asn, Pro or hydroxy-Pro; Xaa5 is Ser, Thr, Gly, Glu, Gla, Asn, Trp (D or L), neo-Trp, halo-Trp, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa6 is Asp, Asn, His, halo-His, Thr, Ser, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa7 is Pro or hydroxy-Pro; Xaa8 is Ala, Ser, Thr, Asp, Val, Ile, Pro, hydroxy-Pro, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa9 is Gly, Ile, Leu, Val, Ala, Thr, Ser, Pro, hydroxy-Pro, Phe, Trp (D or L), neo-Trp, halo-Trp, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid or any unnatural aromatic amino acid; Xaa10 is Ala, Asn, Phe, Pro, hydroxy-Pro, Glu, Gla, Gln, His, halo-His, Val, Ser, Thr, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa11 is Thr, Ser, His, halo-His, Leu, Ile, Val, Asn, Met, Pro, hydroxy-Pro, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa12 is Asn, Pro, hydroxy-Pro, Gln, Ser, Thr, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys N,N,N-trimethyl-Lys, any unnatural basic amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa13 is des-Xaa13, Gly, Thr, Ser, Pro, hydroxy-Pro, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa14 is des-Xaa14, Ile, Val, Asp, Leu, Phe, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; and Xaa15 is des-Xaa15, Gly, Ala, Met, Ser, Thr, Trp (D or L), neo-Trp, halo-Trp, any unnatural aromatic amino acid, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa16 is des-Xaa16, Trp (D or L), neo-Trp, halo-Trp, any unnatural aromatic amino acid, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa12 is des-Xaa17, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid. The C-terminus may contain a free carboxyl group or an amide group. The halo is preferably bromine, chlorine or iodine, more preferably iodine for His or Tyr and bromine for Trp. The Cys residues may be in D or L configuration and may optionally be substituted with homocysteine (D or L). The Tyr residues may be substituted with the 3-hydroxyl or 2-hydroxyl isomers and corresponding O-sulpho- and O-phospho-derivatives. The acidic amino acid residues may be substituted with any synthetic acidic bioisoteric amino acid surrogate, e.g., tetrazolyl derivatives of Gly and Ala.
[0017] More specifically, the present invention is directed to α-conotoxin peptides having the general formula III:
[0018] Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Cys-Cys-Xaa6- -Xaa7-Xaa8-Xaa9-Cys-Xaa10-Xaa11-Xaa12-Xaa.su- b.13-Xaa14-Xaa15-Xaa16-Cys-Xaa17-Xaa18-Xaa19- -Xaa20-Xaa21-Xaa22-Xaa23-Xaa24 (SEQ ID NO:3), wherein Xaa1 is des-Xaa1, Ser or Thr; Xaa2 is des-Xaa2, Asp, Glu, γ-carboxy-Glu (Gla), Asn, Ser or Thr; Xaa3 is des-Xaa3, Ala, Gly, Asn, Ser, Thr, Pro, hydroxy-Pro, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa4 is des-Xaa4, Ala, Val, Leu, Ile, Gly, Glu, Gla, Gln, Asp, Asn, Phe, Pro, hydroxy-Pro or any unnatural aromatic amino acid; Xaa5 is des-Xaa5, Thr, Ser, Asp, Glu, Gla, Gln, Gly, Val, Asp, Asn, Ala, Pro, hydroxy-Pro, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa6 is Thr, Ser, Asp, Asn, Met, Val, Ala, Gly, Leu, Ile, Phe, any unnatural aromatic amino acid, Pro, hydroxy-Pro, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa7 is Ile, Leu, Val, Ser, Thr, Gln, Asn, Asp, Arg, His, halo-His, Phe, any unnatural aromatic amino acid, homoarginine, ornithine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa8 is Pro, hydroxy-Pro, Ser, Thr, Ile, Asp, Leu, Val, Gly, Ala, Phe, any unnatural aromatic amino acid, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa9 is Val, Ala, Gly, Ile, Leu, Asp, Ser, Thr, Pro, hydroxy-Pro, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa10 is His, halo-His, Arg, homoarginine, ornithine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid, Asn, Ala, Ser, Thr, Phe, Ile, Leu, Gly, Trp (D or L), neo-Trp, halo-Trp, any unnatural aromatic amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa11 is Leu, Gln, Val, Ile, Gly, Met, Ala, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, Ser, Thr, Arg, homoarginine, ornithine, any unnatural basic amino acid, Asn, Glu, Gla, Gln, Phe, Trp (D or L), neo-Trp, halo-Trp or any unnatural aromatic amino acid; Xaa12 is Glu, Gla, Gln, Asn, Asp, Pro, hydroxy-Pro, Ser, Gly, Thr, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, Arg, homoarginine, ornithine, any unnatural basic amino acid, Phe, His, halo-His, any unnatural aromatic amino acid, Leu, Met, Gly, Ala, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa13 is His, halo-His, Asn, Thr, Ser, Ile, Val, Leu, Phe, any unnatural aromatic amino acid, Arg, homoarginine, ornithine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid, Tyr, nor-Try, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa14 is Ser, Thr, Ala, Gln, Pro, hydroxy-Pro, Gly, Ile, Leu, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa15 is Asn, Glu, Gla, Asp, Gly, His, halo-His, Ala, Leu, Gln, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa16 is Met, Ile, Thr, Ser, Val, Leu, Pro, hydroxy-Pro, Phe, any unnatural aromatic amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr, any unnatural hydroxy containing amino acid, Glu, Gla, Ala, His, halo-His, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa17 is des-Xaa17, Gly, Asp, Asn, Ala, Ile, Leu, Ser, Thr, His, halo-His, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa18 is des-Xaa18, Gly, Glu, Gla, Gln, Trp (D or L), neo, halo-Trp, any unnatural aromatic amino acid, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa19 is des-Xaa19, Ser, Thr, Val, Ile, Ala, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa20 is des-Xaa20, Val, Asp, His, halo-His, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa21 is des-Xaa21, Asn, Pro or hydroxy-Pro; Xaa22 is des-Xaa22, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa23 is des-Xaa23, Ser or Thr; Xaa24 is des-Xaa24, Leu, Ile or Val; with the proviso that (a) Xaa5 is not Gly, when Xaa1 is des-Xaa1, Xaa2 is des-Xaa2, Xaa3 is des-Xaa3, Xaa4 is des-Xaa4, Xaa6 is Ser, Xaa7 is His, Xaa8 is Pro, Xaa9 is Ala, Xaa10 is Ser, Xaa11 is Val, Xaa12 is Asn, Xaa13 is Asn, Xaa14 is Pro, Xaa15 is Asp, Xaa16 is Ile, Xaa17 is des-Xaa17, Xaa18 is des-Xaa18, Xaa19 is des-Xaa19, Xaa20 is des-Xaa20, Xaa21 is des-Xaa21, Xaa22 is des-Xaa22, Xaa23 is des-Xaa23, and Xaa24 is des-Xaa24. The C-terminus may contain a free carboxyl group or an amide group. The halo is preferably bromine, chlorine or iodine, more preferably iodine for His and Tyr and bromine for Trp. The Cys residues may be in D or L configuration and may optionally be substituted with homocysteine (D or L). The Tyr residues may be substituted with the 3-hydroxyl or 2-hydroxyl isomers and corresponding O-sulpho- and O-phospho-derivatives. The acidic amino acid residues may be substituted with any synthetic acidic bioisoteric amino acid surrogate, e.g., tetrazolyl derivatives of Gly and Ala.
[0019] The present invention is also directed to novel specific α-conotoxin peptides of general formula I having the formulas:
TABLE-US-00001 (SEQ ID NO: 4) Asp-Xaa1-Cys-Cys-Ser-Asp-Ser-Arg-Cys-Gly-Xaa2- Asn-Cys-Leu; (SEQ ID NO: 5) Ala-Cys-Cys-Ser-Asp-Arg-Arg-Cys-Arg-Xaa3-Arg- Cys; (SEQ ID NO: 6) Phe-Thr-Cys-Cys-Arg-Arg-Gly-Thr-Cys-Ser-Gln- His-Cys; (SEQ ID NO: 7) Asp-Xaa4-Cys-Cys-Arg-Arg-His-Ala-Cys-Thr-Leu- Ile-Cys; (SEQ ID NO: 8) Asp-Xaa4-Cys-Cys-Arg-Xaa5-Xaa5-Cys-Thr-Leu- Ile-Cys; (SEQ ID NO: 9) Gly-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Arg-Xaa4- Arg-Cys-Arg; (SEQ ID NO: 10) Gly-Gly-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ala- Xaa3-Arg-Cys; (SEQ ID NO: 11) Ile-Ala-Xaa3-Asp-Ile-Cys-Cys-Ser-Xaa1-Xaa5- Asp-Cys-Asn-His-Xaa2-Cys-Val; and (SEQ ID NO: 12) Gly-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Xaa2-His- Gln-Cys,
wherein Xaa1 is Glu or γ-carboxy-Glu (Gla); Xaa2 is Lys, N-methyl-Lys, N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa3 is Trp (D or L), halo-Trp or neo-Trp; Xaa4 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr; and Xaa5 is Pro or hydroxy-Pro; and the C-terminus contains a carboxyl or amide group. The halo is preferably bromine, chlorine or iodine, more preferably iodine for Tyr and bromine for Trp. In addition, the His residues may be substituted with halo-His; the Arg residues may be substituted by Lys, ornithine, homoarginine, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; the Lys residues may be substituted by Arg, ornithine, homoarginine, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; the Tyr residues may be substituted with any unnatural hydroxy containing amino acid; the Ser residues may be substituted with Thr; the Thr residues may be substituted with Ser; and the Phe and Trp residues may be substituted with any unnatural aromatic amino acid. The Cys residues may be in D or L configuration and may optionally be substituted with homocysteine (D or L). The Tyr residues may be substituted with the 3-hydroxyl or 2-hydroxyl isomers and corresponding O-sulpho- and O-phospho-derivatives. The acidic amino acid residues may be substituted with any synthetic acidic bioisoteric amino acid surrogate, e.g., tetrazolyl derivatives of Gly and Ala.
[0020] More specifically, the present invention is directed to the following α-conotoxin peptides of general formula I:
[0021] Im1.1: SEQ ID NO:4, wherein Xaa1 is Glu and Xaa2 is Lys;
[0022] Im1.2: SEQ ID NO:5, wherein Xaa3 is Trp;
[0023] Rg1.2: SEQ ID NO:6;
[0024] Rg1.6: SEQ ID NO:7, wherein Xaa4 is Tyr;
[0025] Rg1.6A: SEQ ID NO:8, wherein Xaa4 is Tyr and Xaa5 is Pro;
[0026] Rg1.7: SEQ ID NO:9, wherein Xaa4 is Tyr and Xaa5 is Pro;
[0027] Rg1.9: SEQ ID NO:10, wherein Xaa3 is Trp and Xaa5 is Pro;
[0028] Rg1.10: SEQ ID NO:11, wherein Xaa1 is Glu, Xaa2 is Lys, Xaa3 is Trp and Xaa5 is Pro; and
[0029] Rg1.11: SEQ ID NO:12, wherein Xaa2 is Lys and Xaa5 is Pro. The C-terminus of Im1.1, Rg1.7 an Rg1.10 preferably contains a free carboxyl group. The C-terminus of Im1.2, Rg1.2, Rg1.6, Rg1.6A, Rg1.9 and Rg1.11 preferably contains an amide group.
[0030] The present invention is further directed to novel specific α-conotoxin peptides of general formula II having the formulas:
TABLE-US-00002 (SEQ ID NO: 13) Cys-Cys-Ser-Asp-Xaa5-Ala-Cys-Xaa2-Gln-Thr-Xaa5-Gly-Cys-Arg; (SEQ ID NO: 14) Cys-Cys-Xaa1-Asn-Xaa5-Ala-Cys-Arg-His-Thr-Gln-Gly-Cys; (SEQ ID NO: 15) Gly-Cys-Cys-Xaa3-His-Xaa5-Ala-Cys-Gly-Arg-His-Xaa4-Cys; (SEQ ID NO: 16) Ala-Xaa5-Cys-Cys-Asn-Asn-Xaa5-Ala-Cys-Val-Xaa2-His-Arg-Cys; (SEQ ID NO: 17) Ala-Xaa5-Gly-Cys-Cys-Asn-Asn-Xaa5-Ala-Cys-Val-Xaa2-His-Arg-- Cys; (SEQ ID NO: 18) Xaa5-Xaa5-Cys-Cys-Asn-Asn-Xaa5-Ala-Cys-Val-Xaa2-His-Ar- g-Cys; (SEQ ID NO: 19) Asp-Xaa1-Asn-Cys-Cys-Xaa3-Asn-Xaa5-Ser-Cys-Xaa5-Arg-Xa- a5-Arg-Cys-Thr; (SEQ ID NO: 20) Gly-Cys-Cys-Ser-Thr-Xaa5-Xaa5-Cys-Ala-Val-Leu-Xaa4-Cys; (SEQ ID NO: 21) Gly-Cys-Cys-Gly-Asn-Xaa5-Asp-Cys-Thr-Ser-His-Ser-Cys; (SEQ ID NO: 42) Gly-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ala-His-Asn-Asn-Xaa5-Asp-- Cys-Arg; (SEQ ID NO: 154) Gly-Cys-Cys-Xaa4-Asn-Xaa5-Val-Cys-Xaa2-Xaa2-Xaa4-- Xaa4-Cys-Xaa3-Xaa2; (SEQ ID NO: 155) Xaa6-Xaa1-Xaa5-Gly-Cys-Cys-Arg-His-Xaa5-Ala-Cys-Gly-Xa- a2-Asn-Arg-Cys; (SEQ ID NO: 156) Cys-Cys-Ala-Asp-Xaa5-Asp-Cys-Arg-Phe-Arg-Xaa5-Gly-Cys; (SEQ ID NO: 157) Gly-Cys-Cys-Xaa4-Asn-Xaa5-Ser-Cys-Xaa3-Xaa5-Xaa2-- Thr-Xaa4-Cys-Ser-Xaa3-Xaa2; (SEQ ID NO: 158) Cys-Cys-Ser-Asn-Xaa5-Thr-Cys-Xaa2-Xaa1-Thr-Xaa4-Gly-Cy- s; (SEQ ID NO: 159) Cys-Cys-Ala-Asn-Xaa5-Ile-Cys-Xaa2-Asn-Thr-Xaa5-Gly-Cys; (SEQ ID NO: 160) Cys-Cys-Asn-Asn-Xaa5-Thr-Cys-Xaa2-Xaa1-Thr-Xaa4-Gly-Cy- s; (SEQ ID NO: 161) Cys-Cys-Ser-Asn-Xaa5-Val-Cys-Xaa2-Xaa1-Thr-Xaa4-Gly-Cy- s; (SEQ ID NO: 162) Gly-Gly-Cys-Cys-Ser-Xaa4-Xaa5-Xaa5-Cys-Ile-Ala-Ser-Asn-Xaa.- sub.5-Xaa2-Cys-Gly; (SEQ ID NO: 163) Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Ser-Ala-Met-Ser-Xaa5-Ile-Cys; (SEQ ID NO: 164) Gly-Cys-Cys-Xaa2-Asn-Xaa5-Xaa4-Cys-Gly-Ala-Ser-Xaa2-Th- r-Xaa4-Cys; (SEQ ID NO: 165) Gly-Cys-Cys-Ser-Xaa4-Xaa5-Xaa5-Cys-Phe-Ala-Thr-Asn-Xaa5-Asp-Cys; (SEQ ID NO: 166) Gly-Gly-Cys-Cys-Ser-Xaa4-Xaa5-Xaa5-Cys-Ile-Ala-Asn-Asn-Xaa.- sub.5-Leu-Cys-Ala; (SEQ ID NO: 167) Gly-Gly-Cys-Cys-Ser-Xaa4-Xaa5-Xaa5-Cys-Ile-Ala-Asn-Asn-Xaa.- sub.5-Phe-Cys-Ala; (SEQ ID NO: 168) Asp-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ser-Gln-Asn-Asn-Xaa5-Asp-- Cys-Met; and (SEQ ID NO: 169) Asp-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ala-His-Asn-Asn-Xaa5-Asp-- Cys-Arg,
wherein Xaa1 is Glu or γ-carboxy-Glu (Gla); Xaa2 is Lys, N-methyl-Lys, N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa3 is Trp (D or L), halo-Trp or neo-Trp; Xaa4 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr; and Xaa5 is Pro or hydroxy-Pro; and the C-terminus contains a carboxyl or amide group. The halo is preferably bromine, chlorine or iodine, more preferably iodine for Tyr and bromine for Trp. In addition, the His residues may be substituted with halo-His; the Arg residues may be substituted by Lys, ornithine, homoarginine, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; the Lys residues may be substituted by Arg, ornithine, homoarginine, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; the Tyr residues may be substituted with any unnatural hydroxy containing amino acid; the Ser residues may be substituted with Thr; the Thr residues may be substituted with Ser; and the Phe and Trp residues may be substituted with any unnatural aromatic amino acid. The Cys residues may be in D or L configuration and may optionally be substituted with homocysteine (D or L). The Tyr residues may be substituted with the 3-hydroxyl or 2-hydroxyl isomers and corresponding O-sulpho- and O-phospho-derivatives. The acidic amino acid residues may be substituted with any synthetic acidic bioisoteric amino acid surrogate, e.g., tetrazolyl derivatives of Gly and Ala.
[0031] More specifically, the present invention is directed to the following α-conotoxin peptides of general formula II:
[0032] Sn1.1: SEQ ID NO:13, wherein Xaa2 is Lys and Xaa5 is Pro;
[0033] Sn1.2: SEQ ID NO:14, wherein Xaa1 is Glu and Xaa5 is Pro;
[0034] S11.3: SEQ ID NO:15, wherein Xaa3 is Trp, Xaa4 is Tyr and Xaa5 is Pro;
[0035] A1.2: SEQ ID NO:16, wherein Xaa2 is Lys and Xaa5 is Pro;
[0036] Bul.1: SEQ ID NO:17, wherein Xaa2 is Lys and Xaa5 is Pro;
[0037] Bul.2: SEQ ID NO:18, wherein Xaa2 is Lys and Xaa5 is Pro;
[0038] Bul.3: SEQ ID NO:19, wherein Xaa1 is Glu, Xaa3 is Trp and Xaa5 is Pro;
[0039] Bul.4: SEQ ID NO:20, wherein Xaa4 is Tyr and Xaa5 is Pro;
[0040] Cr1.3: SEQ ID NO:21, wherein Xaa5 is Pro;
[0041] Di1.1: SEQ ID NO:42 wherein Xaa5 is Pro;
[0042] Ms1.7: SEQ ID NO:154, wherein Xaa2 is Lys, Xaa3 is Trp, Xaa4 is Tyr and Xaa5 is Pro;
[0043] P1.7: SEQ ID NO:155, wherein Xaa1 is Glu, Xaa2 is Lys, Xaa5 is Pro and Xaa6 is Gln;
[0044] Ms1.2: SEQ ID NO:156, wherein Xaa5 is Pro;
[0045] Ms1.3: SEQ ID NO:157, wherein Xaa2 is Lys, Xaa3 is Trp, Xaa4 is Tyr and Xaa5 is Pro;
[0046] Ms1.4: SEQ ID NO:158, wherein Xaa1 is Glu, Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro;
[0047] Ms1.5: SEQ ID NO:159, wherein Xaa2 is Lys and Xaa5 is Pro;
[0048] Ms1.8: SEQ ID NO:160, wherein Xaa1 is Glu, Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro;
[0049] Ms1.9: SEQ ID NO:161, wherein Xaa1 is Glu, Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro;
[0050] Bt1.7: SEQ ID NO:162, wherein Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro;
[0051] Lv1.5: SEQ ID NO:163, wherein Xaa5 is Pro;
[0052] Ms1.10: SEQ ID NO:164, wherein Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro;
[0053] Om1.1: SEQ ID NO:165, wherein Xaa4 is Tyr and Xaa5 is Pro;
[0054] R1.6: SEQ ID NO:166, wherein Xaa4 is Tyr and Xaa5 is Pro;
[0055] R1.7: SEQ ID NO:167, wherein Xaa4 is Tyr and Xaa5 is Pro;
[0056] Vr1.1: SEQ ID NO:168, wherein Xaa5 is Pro; and
[0057] Vr1.2: SEQ ID NO:169, wherein Xaa5 is Pro. The C-terminus preferably contains a carboxyl group for the peptides Sn1.1, Sn1.2, Cr1.3, Di1.1, Ms1.2, Ms1.4, Ms1.5, Ms1.8, Ms1.9, Vr1.1 and Vr1.2. The C-terminus of the other peptides preferably contains an amide group.
[0058] The present invention is also directed to novel specific α-conotoxin peptides of general formula III having the formulas:
TABLE-US-00003 (SEQ ID NO: 22) Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa1-His-Ser-Asn-Met-Cy- s; (SEQ ID NO: 23) Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-Arg-Gln-Asn-Asn-Ala-Xaa1-Xaa.su- b.4-Cys-Arg; (SEQ ID NO: 24) Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-- Xaa1-Ile-Cys-Arg; (SEQ ID NO: 25) Xaa5-Xaa1-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa.- sub.5-Xaa1-Ile-Cys-Arg; (SEQ ID NO: 26) Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-- Xaa1-Ile-Cys-Asp; (SEQ ID NO: 27) Xaa5-Arg-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-- Xaa1-Ile-Cys-Arg; (SEQ ID NO: 28) Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-- Gly-Ile-Cys-Arg; (SEQ ID NO: 29) Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-- Xaa1-Thr-Cys-Arg; (SEQ ID NO: 30) Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-- Xaa1-Val-Cys-Arg; (SEQ ID NO: 31) Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Ile-Asp-His-Xaa5-- Xaa1-Ile-Cys-Arg; (SEQ ID NO: 32) Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-- Xaa1-Ile-Cys-Arg- Arg-Arg-Arg; (SEQ ID NO: 33) Gly-Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Val-Asn-His-Xaa5-Xaa.su- b.1-Leu-Cys; (SEQ ID NO: 34) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Val-Asn-His-Xaa5-Xaa1-- Leu-Cys; (SEQ ID NO: 35) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-- Ile-Cys; (SEQ ID NO: 36) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Xaa2-Thr-Gln-Xaa1-- Xaa5-Cys-Arg-Xaa1- Ser; (SEQ ID NO: 37) Xaa5-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Asn-Asn-Xaa5-Xaa.- sub.1-Phe-Cys-Arg-Gln; (SEQ ID NO: 38) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Asn-Asn-Xaa5-Xaa1-- Phe-Cys-Arg-Gln; (SEQ ID NO: 39) Gly-Cys-Cys-Ser-His-Xaa5-Xaa5-Cys-Ala-Met-Asn-Asn-Xaa5-Asp-- Xaa4-Cys; (SEQ ID NO: 40) Gly-Cys-Cys-Ser-His-Xaa5-Xaa5-Cys-Phe-Leu-Asn-Asn-Xaa5-Asp-- Xaa4-Cys; (SEQ ID NO: 41) Gly-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ile-Ala-Xaa2-Asn-Xaa5-His-Met-Cys-Gly; (SEQ ID NO: 43) Gly-Cys-Cys-Ser-Asn-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Xaa5-His-Val-Cy- s-Arg-Gln; (SEQ ID NO: 44) Gly-Cys-Cys-Ser-Arg-Xaa5-Ala-Cys-Ile-Ala-Asn-Asn-Xaa5-Asp-Leu-Cy- s; (SEQ ID NO: 45) Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Val-Xaa1-His-Xaa5- -Xaa1-Leu-Cys-Arg-Arg- Arg-Arg; (SEQ ID NO: 46) Gly-Gly-Cys-Cys-Ser-Phe-Xaa5-Ala-Cys-Arg-Xaa2-Xaa5-Arg-Xaa.- sub.5-Xaa1-Met-Cys-Gly; (SEQ ID NO: 47) Xaa5-Xaa1-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Ser-Ser-His-Xaa.- sub.5-Xaa1-Leu-Cys-Gly; (SEQ ID NO: 48) Xaa5-Gln-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Val-Gly-His-Xaa5-- Xaa1-Leu-Cys-Gly; (SEQ ID NO: 49) Xaa6-Val-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Val-Gly-His-Xaa5-- Xaa1-Ile-Cys-Gly; (SEQ ID NO: 50) Gly-Cys-Cys-Ser-Arg-Xaa5-Xaa5-Cys-Ile-Ala-Asn-Asn-Xaa5-Asp-- Leu-Cys; (SEQ ID NO: 51) Xaa5-Gln-Cys-Cys-Ser-His-Leu-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa.su- b.1-Ile-Cys-Arg; (SEQ ID NO: 52) Gly-Cys-Cys-Ser-Xaa4-Phe-Asp-Cys-Arg-Met-Met-Phe-Xaa5-Xaa1-- Met-Cys-Gly-Xaa3- Arg; (SEQ ID NO: 53) Gly-Gly-Cys-Cys-Ser-Phe-Ala-Ala-Cys-Arg-Xaa2-Xaa4-Arg-Xaa5-- Xaa1-Met-Cys-Gly; (SEQ ID NO: 54) Gly-Gly-Cys-Cys-Phe-His-Xaa5-Val-Cys-Xaa4-Ile-Asn-Leu-Leu-Xaa.su- b.1-Met-Cys-Arg- Gln-Arg; (SEQ ID NO: 55) Ser-Ala-Thr-Cys-Cys-Asn-Xaa4-Xaa5-Xaa5-Cys-Xaa4-Xaa.su- b.1-Thr-Xaa4-Xaa5-Xaa1-Ser- Cys-Leu; (SEQ ID NO: 56) Ala-Cys-Cys-Ala-Xaa4-Xaa5-Xaa5-Cys-Phe-Xaa1-Ala-Xaa.su- b.4-Xaa5-Xaa1-Arg-Cys-Leu; (SEQ ID NO: 57) Asn-Ala-Xaa1-Cys-Cys-Xaa4-Xaa4-Xaa5-Xaa5-Cys-Xaa.- sub.4-Xaa1-Ala-Xaa4-Xaa5-Xaa1-Ile- Cys-Leu; (SEQ ID NO: 170) Xaa1-Cys-Cys-Thr-Asn-Xaa5-Val-Cys-His-Ala-Xaa1-His-Gln-Xaa.- sub.1-Leu-Cys-Ala-Arg- Arg-Arg; (SEQ ID NO: 171) Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa1-His-Ser-Asn-Leu-Cy- s; (SEQ ID NO: 172) Xaa1-Cys-Cys-Thr-Asn-Xaa5-Val-Cys-His-Val-Xaa1-His-Gln-Xaa.- sub.1-Leu-Cys-Ala-Arg- Arg-Arg; (SEQ ID NO: 173) Xaa6-Xaa1-Cys-Cys-Ser-Xaa4-Xaa5-Ala-Cys-Asn-Leu-Asp-Hi- s-Xaa5-Xaa1-Leu-Cys; (SEQ ID NO: 174) Xaa5-Xaa1-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Ser-Thr-His-Xaa.- sub.5-Xaa1-Leu-Cys-Gly; (SEQ ID NO: 175) Leu-Asn-Cys-Cys-Met-Ile-Xaa5-Xaa5-Cys-Xaa3-Xaa2-Xaa.su- b.2-Xaa4-Gly-Asp-Arg-Cys-Ser- Xaa1-Val-Arg; (SEQ ID NO: 176) Ala-Phe-Gly-Cys-Cys-Asp-Leu-Ile-Xaa5-Cys-Leu-Xaa1-Arg-Xaa4-- Gly-Asn-Arg-Cys- Asn-Xaa1-Val-His; (SEQ ID NO: 177) Leu-Gly-Cys-Cys-Asn-Val-Thr-Xaa5-Cys-Xaa3-Xaa1-Xaa2-Xa- a4-Gly-Asp-Xaa2-Cys- Asn-Xaa1-Val-Arg; (SEQ ID NO: 178) Asp-Xaa1-Cys-Cys-Ser-Asn-Xaa5-Ala-Cys-Arg-Val-Asn-Asn-Xaa5-- His-Val-Cys-Arg- Arg-Arg; (SEQ ID NO: 179) Leu-Asn-Cys-Cys-Ser-Ile-Xaa5-Gly-Cys-Xaa3-Asn-Xaa1-Xaa4-Xaa2-Asp-Arg-Cys-Ser- Xaa2-Val-Arg; (SEQ ID NO: 180) Gly-Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Xaa4-Phe-Asn-Asn-Xaa5-- Gln-Met-Cys-Arg; (SEQ ID NO: 181) Gly-Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Asn-Leu-Asn-Asn-Xaa5-Gln-Me- t-Cys-Arg; (SEQ ID NO: 182) Gly-Cys-Cys-Ser-His-Xaa5-Xaa5-Cys-Xaa4-Ala-Asn-Asn-Gln-Ala-- Xaa4-Cys-Asn; (SEQ ID NO: 183) Gly-Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Val-Thr-His-Xaa5-Xaa.su- b.1-Leu-Cys; (SEQ ID NO: 184) Gly-Gly-Cys-Cys-Ser-Xaa4-Xaa5-Ala-Cys-Ser-Val-Xaa1-His-Gln-- Asp-Leu-Cys-Asp; (SEQ ID NO: 185) Val-Ser-Cys-Cys-Val-Val-Arg-Xaa5-Cys-Xaa3-Ile-Arg-Xaa4-Gln-- Xaa1-Xaa1-Cys-Leu- Xaa1-Ala-Asp-Xaa5-Arg-Thr-Leu; (SEQ ID NO: 186) Xaa6-Asn-Cys-Cys-Ser-Ile-Xaa5-Gly-Cys-Xaa3-Xaa1-Xaa.su- b.2-Xaa4-Gly-Asp-Xaa2-Cys-Ser- Xaa1-Val-Arg; (SEQ ID NO: 187) Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa1-His-Xaa5-Asn-- Ala-Cys; (SEQ ID NO: 188) Gly-Cys-Cys-Ser-Asn-Xaa5-Ile-Cys-Xaa4-Phe-Asn-Asn-Xaa5-Arg-- Ile-Cys-Arg; (SEQ ID NO: 189) Xaa1-Cys-Cys-Ser-Gln-Xaa5-Xaa5-Cys-Arg-Xaa3-Xaa2--
His-Xaa5-Xaa1-Leu-Cys-Ser; (SEQ ID NO: 190) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Gln-His-Ile-Cys; (SEQ ID NO: 191) Gly-Cys-Cys-Ala-Val-Xaa5-Ser-Cys-Arg-Leu-Arg-Asn-Xaa5-Asp-Leu-Cy- s-Gly-Gly; (SEQ ID NO: 192) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asn-Asn-Xaa5-His-Ile-Cy- s; (SEQ ID NO: 193) Thr-Xaa5-Xaa1-Xaa1-Cys-Cys-Xaa5-Asn-Xaa5-Xaa5-Cys-Phe-Ala-Thr-Asn-Ser-Asp-Ile- Cys-Gly; (SEQ ID NO: 194) Asp-Ala-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Gly-Xaa2-His-Gln-Asp-Le- u-Cys; (SEQ ID NO: 195) Xaa1-Asp-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Val-Gly-His-Gln-Asp-Le- u-Cys; (SEQ ID NO: 196) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Ser-Asn-Ala-His-Ile-Cys; (SEQ ID NO: 197) Xaa1-Asp-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Val-Gly-His-Gln-Asp-Me- t-Cys; (SEQ ID NO: 198) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Xaa5-His-Ile-Cy- s; (SEQ ID NO: 199) Gly-Cys-Cys-Gly-Asn-Xaa5-Ser-Cys-Ser-Ile-His-Ile-Xaa5-Xaa4-- Val-Cys-Asn; (SEQ ID NO: 200) Thr-Asp-Ser-Xaa1-Xaa1-Cys-Cys-Leu-Asp-Ser-Arg-Cys-Ala-Gly-Gln-Hi- s-Gln-Asp- Leu-Cys-Gly; (SEQ ID NO: 201) Gly-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Xaa4-Ala-Asn-Asn-Gln-Ala-- Xaa4-Cys-Asn; (SEQ ID NO: 202) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Val-Asn-Asn-Xaa5-Asp-Ile-Cy- s; (SEQ ID NO: 203) Gly-Xaa2-Cys-Cys-Ile-Asn-Asp-Ala-Cys-Arg-Ser-Xaa2-His-Xaa5-- Gln-Xaa4-Cys-Ser; (SEQ ID NO: 204) Gly-Cys-Cys-Xaa4-Asn-Ile-Ala-Cys-Arg-Ile-Asn-Asn-Xaa5-Arg-Xaa.su- b.4-Cys-Arg; (SEQ ID NO: 205) Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Arg-Phe-Asn-Xaa4-Xaa5-Xaa.- sub.2-Xaa4-Cys-Gly; (SEQ ID NO: 206) Asp-Xaa1-Cys-Cys-Ala-Ser-Xaa5-Xaa5-Cys-Arg-Leu-Asn-Asn-Xaa.- sub.5-Xaa4-Val-Cys-His; (SEQ ID NO: 207) Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-Xaa3-Gln-Asn-Asn-Ala-Xaa1-- Xaa4-Cys-Arg-Xaa1- Ser; (SEQ ID NO: 208) Gly-Cys-Cys-Ser-His-Xaa5-Xaa5-Cys-Ala-Gln-Asn-Asn-Gln-Asp-Xaa.su- b.4-Cys; (SEQ ID NO: 209) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Asn-Asn-Arg-Xaa1-Xaa.su- b.4-Cys-Arg-Xaa1- Ser; (SEQ ID NO: 210) Asp-Xaa5-Cys-Cys-Ser-Xaa4-Xaa5-Asp-Cys-Gly-Ala-Asn-His-Xaa.- sub.5-Xaa1-Ile-Cys-Gly; (SEQ ID NO: 211) Xaa1-Cys-Cys-Ser-Gln-Xaa5-Xaa5-Cys-Arg-Xaa3-Xaa2-- His-Xaa5-Xaa1-Leu-Cys-Ser; (SEQ ID NO: 212) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Xaa5-His-Ile-Cy- s; (SEQ ID NO: 213) Gly-Cys-Cys-Ser-Asp-Xaa5-Ser-Cys-Asn-Val-Asn-Asn-Xaa5-Asp-Xaa.su- b.4-Cys; (SEQ ID NO: 214) Xaa1-Xaa1-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Val-Gly-His-Gln-- Asp-Met-Cys-Arg; (SEQ ID NO: 215) Gly-Gly-Cys-Cys-Ser-Asn-Xaa5-Ala-Cys-Leu-Val-Asn-His-Leu-Xaa1-Me- t-Cys; (SEQ ID NO: 216) Arg-Asp-Xaa5-Cys-Cys-Phe-Asn-Xaa5-Ala-Cys-Asn-Val-Asn-Asn-Xaa.su- b.5-Gln-Ile-Cys; (SEQ ID NO: 217) Cys-Cys-Ser-Asp-Xaa5-Ser-Cys-Xaa3-Arg-Leu-His-Ser-Leu-Ala-Cys-Th- r-Gly-Ile-Val- Asn-Arg; (SEQ ID NO: 218) Cys-Cys-Thr-Asn-Xaa5-Ala-Cys-Leu-Val-Asn-Asn-Ile-Arg-Phe-Cys-Gly; (SEQ ID NO: 219) Asp-Xaa1-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-His-Gly-Asn-Asn-Arg-Asp-Hi- s-Cys-Ala; (SEQ ID NO: 220) Asp-Cys-Cys-Ser-His-Xaa5-Leu-Cys-Arg-Leu-Phe-Val-Xaa5-Gly-Leu-Cy- s-Ile; (SEQ ID NO: 221) Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Xaa2-Val-Arg-Xaa4-Xaa5-Asp-Leu-Cys-Arg; (SEQ ID NO: 222) Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asn-Asn-Xaa5-His-Ile-Cy- s; (SEQ ID NO: 223) Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Xaa2-Val-Arg-Xaa4-Ser-Asp-- Met-Cys; (SEQ ID NO: 224) Gly-Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Xaa2-Val-His-Phe-Xaa5-- His-Ser-Cys; (SEQ ID NO: 225) Val-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Val-Asp-His-Xaa5-Xaa1-- Leu-Cys-Arg-Arg- Arg-Arg; (SEQ ID NO: 226) Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Asn-Leu-Ser-Asn-Xaa5-Gln-Ile-Cy- s-Arg; (SEQ ID NO: 227) Xaa6-Xaa1-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa.- sub.5-Xaa1-Ile-Cys-Arg; (SEQ ID NO: 228) Gly-Cys-Cys-Ser-Asn-Xaa5-Ala-Cys-Leu-Val-Asn-His-Ile-Arg-Phe-Cys-Gly; (SEQ ID NO: 229) Asp-Cys-Cys-Asp-Asp-Xaa5-Ala-Cys-Thr-Val-Asn-Asn-Xaa5-Gly-Leu-Cy- s-Thr; and (SEQ ID NO: 230) Gly-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ile-Ala-Xaa2-Asn-Xaa5-His-Met-Cys-Gly-Gly- Arg-Arg,
wherein Xaa1 is Glu or γ-carboxy-Glu (Gla); Xaa2 is Lys, N-methyl-Lys, N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa3 is Trp (D or L), halo-Trp or neo-Trp; Xaa4 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr; and Xaa5 is Pro or hydroxy-Pro; Xaa6 is Gln or pyro-Glu; and the C-terminus contains a carboxyl or amide group. The halo is preferably bromine, chlorine or iodine, more preferably iodine for Tyr and bromine for Trp. In addition, the His residues may be substituted with halo-His; the Arg residues may be substituted by Lys, ornithine, homoarginine, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; the Lys residues may be substituted by Arg, ornithine, homoarginine, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; the Tyr residues may be substituted with any unnatural hydroxy containing amino acid; the Ser residues may be substituted with Thr; the Thr residues may be substituted with Ser; and the Phe and Trp residues may be substituted with any unnatural aromatic amino acid. The Cys residues may be in D or L configuration and may optionally be substituted with homocysteine (D or L). The Tyr residues may be substituted with the 3-hydroxyl or 2-hydroxyl isomers and corresponding O-sulpho- and O-phospho-derivatives. The acidic amino acid residues may be substituted with any synthetic acidic bioisoteric amino acid surrogate, e.g., tetrazolyl derivatives of Gly and Ala.
[0059] More specifically, the present invention is directed to the following α-conotoxin peptides of general formula III:
[0060] SmI: SEQ ID NO:22, wherein Xaa1 is Glu and Xaa5 is Pro;
[0061] OB-29: SEQ ID NO:23, wherein Xaa1 is Glu, Xaa3 is Tyr and Xaa5 is Pro;
[0062] Tx1.1: SEQ ID NO:24, wherein Xaa1 is Glu and Xaa5 is Pro;
[0063] R1.1A: SEQ ID NO:25, wherein Xaa1 is Glu and Xaa5 is Pro;
[0064] R1.1B: SEQ ID NO:26, wherein Xaa1 is Glu and Xaa5 is Pro;
[0065] Om-9: SEQ ID NO:27, wherein Xaa1 is Glu and Xaa5 is Pro;
[0066] Om-10: SEQ ID NO:28, wherein Xaa5 is Pro;
[0067] Om-21: SEQ ID NO:29, wherein Xaa1 is Glu and Xaa5 is Pro;
[0068] Om-25: SEQ ID NO:30, wherein Xaa1 is Glu and Xaa5 is Pro;
[0069] Om-27: SEQ ID NO:31, wherein Xaa1 is Glu and Xaa5 is Pro;
[0070] Om-28: SEQ ID NO:32, wherein Xaa1 is Glu and Xaa5 is Pro;
[0071] Bt1.2: SEQ ID NO:33, wherein Xaa1 is Glu and Xaa5 is Pro;
[0072] Bt1.4: SEQ ID NO:34, wherein Xaa1 is Glu and Xaa5 is Pro;
[0073] Da1.1: SEQ ID NO:35, wherein Xaa1 is Glu and Xaa5 is Pro;
[0074] OB-20: SEQ ID NO:36, wherein Xaa1 is Glu, Xaa2 is Lys and Xaa5 is Pro;
[0075] TI: SEQ ID NO:37, wherein Xaa1 is Glu and Xaa5 is Pro;
[0076] TIB: SEQ ID NO:38, wherein Xaa1 is Glu and Xaa5 is Pro;
[0077] Pn1.1: SEQ ID NO:39, wherein Xaa5 is Pro;
[0078] Pn1.2: SEQ ID NO:40, wherein Xaa1 is Glu and Xaa5 is Pro;
[0079] T1: SEQ ID NO:41, wherein Xaa2 is Lys and Xaa5 is Pro;
[0080] TIA: SEQ ID NO:43, wherein Xaa5 is Pro;
[0081] Da1.2: SEQ ID NO:44, wherein Xaa5 is Pro;
[0082] Cr1.2: SEQ ID NO:45, wherein Xaa1 is Glu and Xaa5 is Pro;
[0083] Sl1.2: SEQ ID NO:46, wherein Xaa1 is Glu, Xaa2 is Lys and Xaa5 is Pro;
[0084] Tx1.3: SEQ ID NO:47, wherein Xaa1 is Glu and Xaa5 is Pro;
[0085] Da1.3: SEQ ID NO:48, wherein Xaa1 is Glu and Xaa5 is Pro;
[0086] Da1.4: SEQ ID NO:49, wherein Xaa1 is Glu, Xaa5 is Pro and Xaa6 is Gln;
[0087] Tx1.2: SEQ ID NO:50, wherein Xaa5 is Pro;
[0088] Om-35: SEQ ID NO:51, wherein Xaa1 is Glu and Xaa5 is Pro;
[0089] Sl1.1: SEQ ID NO:52, wherein Xaa1 is Glu, Xaa3 is Trp, Xaa4 is Tyr and Xaa5 is Pro;
[0090] Sl1.6: SEQ ID NO:53, wherein Xaa1 is Glu, Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro;
[0091] Sl1.7: SEQ ID NO:54, wherein Xaa1 is Glu Xaa4 is Tyr and Xaa5 is Pro;
[0092] Bt1.1: SEQ ID NO:55, wherein Xaa1 is Glu Xaa4 is Tyr and Xaa5 is Pro;
[0093] Bt:1.3: SEQ ID NO:56, wherein Xaa1 is Glu Xaa4 is Tyr and Xaa5 is Pro;
[0094] Bt1.5: SEQ ID NO:57, wherein Xaa1 is Glu Xaa4 is Tyr and Xaa5 is Pro;
[0095] A1.4: SEQ ID NO:170, wherein Xaa1 is Glu and Xaa5 is Pro;
[0096] A1.5: SEQ ID NO:171, wherein Xaa1 is Glu and Xaa5 is Pro;
[0097] A1.6: SEQ ID NO:172, wherein Xaa1 is Glu and Xaa5 is Pro;
[0098] Af1.1: SEQ ID NO:173, wherein Xaa1 is Glu Xaa4 is Tyr, Xaa5 is Pro and Xaa6 is Gln;
[0099] Af1.2: SEQ ID NO:174, wherein Xaa1 is Glu and Xaa5 is Pro;
[0100] Ar1.2: SEQ ID NO:175, wherein Xaa1 is Glu, Xaa2 is Lys, Xaa3 is Trp, Xaa4 is Try and Xaa5 is Pro;
[0101] Ar1.3: SEQ ID NO:176, wherein Xaa1 is Glu, Xaa4 is Tyr and Xaa5 is Pro;
[0102] Ar1.4: SEQ ID NO:177, wherein Xaa1 is Glu, Xaa2 is Lys, Xaa3 is Trp, Xaa4 is
[0103] Try and Xaa5 is Pro;
[0104] Ar1.5: SEQ ID NO:178, wherein Xaa1 is Glu and Xaa5 is Pro;
[0105] Ar1.6: SEQ ID NO:179, wherein Xaa1 is Glu, Xaa2 is Lys, Xaa3 is Trp, Xaa4 is Try and Xaa5 is Pro;
[0106] Ay1.2: SEQ ID NO:180, wherein Xaa4 is Tyr and Xaa5 is Pro;
[0107] Ay1.3: SEQ ID NO:181, wherein Xaa5 is Pro;
[0108] Bn1.4: SEQ ID NO:182, wherein Xaa4 is Tyr and Xaa5 is Pro;
[0109] Bt1.8: SEQ ID NO:183, wherein Xaa1 is Glu and Xaa5 is Pro;
[0110] Bt1.9: SEQ ID NO:184, wherein Xaa1 is Glu, Xaa4 is Tyr and Xaa5 is Pro;
[0111] Ca1.3: SEQ ID NO:185, wherein Xaa1 is Glu, Xaa3 is Trp, Xaa4 is Try and Xaa5 is Pro;
[0112] Ca1.4: SEQ ID NO:186, wherein Xaa1 is Glu, Xaa2 is Lys, Xaa3 is Trp, Xaa4 is
[0113] Try, Xaa5 is Pro and Xaa6 is Gln;
[0114] C1.2: SEQ ID NO:187, wherein Xaa1 is Glu and Xaa5 is Pro;
[0115] C1.3: SEQ ID NO:188, wherein Xaa4 is Tyr and Xaa5 is Pro;
[0116] Ep1.2: SEQ ID NO:189, wherein Xaa1 is Glu, Xaa2 is Lys, Xaa3 is Trp and Xaa5 is Pro;
[0117] G1.1: SEQ ID NO:190, wherein Xaa5 is Pro;
[0118] G1.3: SEQ ID NO:191, wherein Xaa5 is Pro;
[0119] Im1.3: SEQ ID NO:192, wherein Xaa5 is Pro;
[0120] Lv1.2: SEQ ID NO:193, wherein Xaa1 is Glu and Xaa5 is Pro;
[0121] Lv1.3: SEQ ID NO:194, wherein Xaa2 is Lys and Xaa5 is Pro;
[0122] Lv1.4: SEQ ID NO:195, wherein Xaa1 is Glu and Xaa5 is Pro;
[0123] Lv1.6: SEQ ID NO:196, wherein Xaa5 is Pro;
[0124] Lv1.7: SEQ ID NO:197, wherein Xaa1 is Glu and Xaa5 is Pro;
[0125] Lv1.8: SEQ ID NO:198, wherein Xaa5 is Pro;
[0126] Lv1.9: SEQ ID NO:199, wherein Xaa4 is Tyr and Xaa5 is Pro;
[0127] Lv1.10: SEQ ID NO:200, wherein Xaa1 is Glu;
[0128] Mr1.3: SEQ ID NO:201, wherein Xaa4 is Tyr and Xaa5 is Pro;
[0129] Mr1.4: SEQ ID NO:202, wherein Xaa5 is Pro;
[0130] Ms1.1: SEQ ID NO:203, wherein Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro;
[0131] Ms1.6: SEQ ID NO:204, wherein Xaa4 is Tyr and Xaa5 is Pro;
[0132] O1.1: SEQ ID NO:205, wherein Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro;
[0133] O1.2: SEQ ID NO:206, wherein Xaa1 is Glu, Xaa4 is Tyr and Xaa5 is Pro;
[0134] O1.4: SEQ ID NO:207, wherein Xaa1 is Glu, Xaa3 is Trp, Xaa4 is Tyr and Xaa5 is Pro;
[0135] O1.7: SEQ ID NO:208, wherein Xaa4 is Tyr and Xaa5 is Pro;
[0136] O1.8: SEQ ID NO:209, wherein Xaa1 is Glu, Xaa4 is Tyr and Xaa5 is Pro;
[0137] Om1.2: SEQ ID NO:210, wherein Xaa1 is Glu, Xaa4 is Tyr and Xaa5 is Pro;
[0138] Om1.3: SEQ ID NO:211, wherein Xaa1 is Glu, Xaa2 is Lys, Xaa3 is Trp and Xaa5 is Pro;
[0139] Om1.4: SEQ ID NO:212, wherein Xaa5 is Pro;
[0140] Om1.5: SEQ ID NO:213, wherein Xaa4 is Tyr and Xaa5 is Pro;
[0141] Om1.6: SEQ ID NO:214, wherein Xaa1 is Glu and Xaa5 is Pro;
[0142] P1.4: SEQ ID NO:215, wherein Xaa1 is Glu and Xaa5 is Pro;
[0143] P1.5: SEQ ID NO:216, wherein Xaa5 is Pro;
[0144] P1.6: SEQ ID NO:217, wherein Xaa3 is Trp and Xaa5 is Pro;
[0145] P1.8: SEQ ID NO:218, wherein Xaa5 is Pro;
[0146] Rg1.1: SEQ ID NO:219, wherein Xaa1 is Glu and Xaa5 is Pro;
[0147] Rg1.3: SEQ ID NO:220, wherein Xaa5 is Pro;
[0148] Rg1.4: SEQ ID NO:221, wherein Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro;
[0149] Rg1.5: SEQ ID NO:222, wherein Xaa5 is Pro;
[0150] Rg1.8: SEQ ID NO:223, wherein Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro;
[0151] Sm1.4: SEQ ID NO:224, wherein Xaa2 is Lys and Xaa5 is Pro;
[0152] Sm1.5: SEQ ID NO:225, wherein Xaa1 is Glu and Xaa5 is Pro;
[0153] S1.5: SEQ ID NO:226, wherein Xaa5 is Pro;
[0154] Tx1.5: SEQ ID NO:227, wherein Xaa1 is Glu, Xaa5 is Pro and Xaa6 is Gln;
[0155] T1.1: SEQ ID NO:228, wherein Xaa5 is Pro;
[0156] Vr1.3: SEQ ID NO:229, wherein Xaa5 is Pro; and
[0157] Tb: SEQ ID NO:230, wherein Xaa2 is Lys and Xaa5 is Pro. The C-terminus preferably contains a carboxyl group for the peptides OB-29, Tx1.1, R1.1A, R1.1B, Om-9, Om-10, Om-21, Om-25, Om-27, Om-28, Cr1.2, Om-35, Bt1.1, Bt1.3, Bt1.5, A1.4, A1.6, Ar1.2, Ar1.3, Ar1.4, Ar1.5, Ar1.6, Ca1.3, Ca1.4, Ep1.2, Lv1.9, 01.2, Om1.3, Om1.6, P1.6, Rg1.1, Rg1.3, Rg1.4, Sm1.5, Tx1.5 and Vr1.3. The C-terminus of the other peptides preferably contains an amide group.
[0158] The present invention is also directed to the novel specific α-conotoxin peptides having the formulas:
TABLE-US-00004 (SEQ ID NO: 231) Cys-Cys-Thr-Ile-Xaa5-Ser-Cys-Xaa4-Xaa1-Xaa2-Xaa2- Xaa2-Ile-Xaa2-Ala-Cys-Val-Phe and (SEQ ID NO: 232) Gly-Cys-Cys-Gly-Asn-Xaa5-Ala-Cys-Ser-Gly-Ser-Ser- Xaa2-Asp-Ala-Xaa5-Ser-Cys,
wherein Xaa1 is Glu or γ-carboxy-Glu (Gla); Xaa2 is Lys, N-methyl-Lys, N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa4 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr; and Xaa5 is Pro or hydroxy-Pro; and the C-terminus contains a carboxyl or amide group. The halo is preferably bromine, chlorine or iodine, more preferably iodine for Tyr. In addition, the His residues may be substituted with halo-His; the Arg residues may be substituted by Lys, ornithine, homoarginine, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; the Lys residues may be substituted by Arg, ornithine, homoarginine, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; the Tyr residues may be substituted with any unnatural hydroxy containing amino acid; the Ser residues may be substituted with Thr; the Thr residues may be substituted with Ser; and the Phe residues may be substituted with any unnatural aromatic amino acid. The Cys residues may be in D or L configuration and may optionally be substituted with homocysteine (D or L). The Tyr residues may be substituted with the 3-hydroxyl or 2-hydroxyl isomers and corresponding O-sulpho- and O-phospho-derivatives. The acidic amino acid residues may be substituted with any synthetic acidic bioisoteric amino acid surrogate, e.g., tetrazolyl derivatives of Gly and Ala.
[0159] More specifically, the present invention is directed to the following α-conotoxin peptides:
[0160] G1.2: SEQ ID NO:231, wherein Xaa1 is Glu, Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro; and
[0161] Rg1.12: SEQ ID NO:232, wherein Xaa2 is Lys and Xaa5 is Pro. The C-terminus of G1.2 preferably contains a carboxyl group, and the C-terminus of Rg1.12 preferably contains an amide group.
[0162] Examples of unnatural aromatic amino acid include, but are not limited to, such as nitro-Phe, 4-substituted-Phe wherein the substituent is C1-C3 alkyl, carboxyl, hydroxymethyl, sulphomethyl, halo, phenyl, --CHO, --CN, --SO3H and --NHAc. Examples of unnatural hydroxy containing amino acid, include, but are not limited to, such as 4-hydroxymethyl-Phe, 4-hydroxyphenyl-Gly, 2,6-dimethyl-Tyr and 5-amino-Tyr. Examples of unnatural basic amino acids include, but are not limited to, N-1-(2-pyrazolinyl)-Arg, 2-(4-piperinyl)-Gly, 2-(4-piperinyl)-Ala, 2-[3-(2S)pyrrolininyl)-Gly and 2-[3-(2S)pyrrolininyl)-Ala. These and other unnatural basic amino acids, unnatural hydroxy containing amino acids or unnatural aromatic amino acids are described in Building Block Index, Version 3.0 (1999 Catalog, pages 4-47 for hydroxy containing amino acids and aromatic amino acids and pages 66-87 for basic amino acids; see also website "amino-acids.com"), incorporated herein by reference, by and available from RSP Amino Acid Analogues, Inc., Worcester, Mass.
[0163] Optionally, in the peptides of general formulas I, II and III and the specific peptides described above, the Asn residues may be modified to contain an N-glycan and the Ser and Thr residues may be modified to contain an O-glycan. In accordance with the present invention, a glycan shall mean any N-, S- or O-linked mono-, di-, tri-, poly- or oligosaccharide that can be attached to any hydroxy, amino or thiol group of natural or modified amino acids by synthetic or enzymatic methodologies known in the art. The monosaccharides making up the glycan can include D-allose, D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose, D-talose, D-galactosamine, D-glucosamine, D-N-acetyl-glucosamine (GlcNAc), D-N-acetyl-galactosamine (GalNAc), D-fucose or D-arabinose. These saccharides may be structurally modified, e.g., with one or more O-sulfate, O-phosphate, O-acetyl or acidic groups, such as sialic acid, including combinations thereof. The glycan may also include similar polyhydroxy groups, such as D-penicillamine 2,5 and halogenated derivatives thereof or polypropylene glycol derivatives. The glycosidic linkage is beta and 1-4 or 1-3, preferably 1-3. The linkage between the glycan and the amino acid may be alpha or beta, preferably alpha and is 1-.
[0164] Core O-glycans have been described by Van de Steen et al. (1998), incorporated herein by reference. Mucin type O-linked oligosaccharides are attached to Ser or Thr (or other hydroxylated residues of the present peptides) by a GalNAc residue. The monosaccharide building blocks and the linkage attached to this first GalNAc residue define the "core glycans," of which eight have been identified. The type of glycosidic linkage (orientation and connectivities) are defined for each core glycan. Suitable glycans and glycan analogs are described further in U.S. Ser. No. 09/420,797, filed 19 Oct. 1999 (now U.S. Pat. No. 6,369,193) and in PCT Application No. PCT/US99/24380, filed 19 Oct. 1999, both incorporated herein by reference. A preferred glycan is Gal(β1→3)GalNAc(α1→).
[0165] Optionally, in the peptides of general formulas I and II and the specific peptides described above, pairs of Cys residues may be replaced pairwise with Ser/(Glu or Asp) or Lys/(Glu or Asp) combinations. Sequential coupling by known methods (Barnay et al., 2000; Hruby et al., 1994; Bitan et al., 1997) allows replacement of native Cys bridges with lactam bridges.
[0166] The present invention is further directed to propeptides and nucleic acid sequences encoding the propeptides or peptides as described in further detail herein.
DETAILED DESCRIPTION OF THE INVENTION
[0167] The invention relates to relatively short peptides (termed α-conotoxins herein), about 10-30 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include two disulfide bonds.
[0168] The present invention, in another aspect, relates to a pharmaceutical composition comprising an effective amount of an α-conotoxin peptide. Such a pharmaceutical composition has the capability of acting as antagonists for nicotinic acetylcholine receptors. In one aspect, the α-conotoxins with specificity for neuromuscular junction nicotinic acetylcholine receptors are used as neuromuscular blocking agents for use in conjunction with surgery, as disclosed in U.S. patent application Ser. No. 09/488,799, filed 21 Jan. 2000, incorporated by reference herein. In a second aspect, additional α-conotoxins and uses for them have been described in U.S. Pat. No. 4,447,356 (Olivera et al., 1984); U.S. Pat. Nos. 5,432,155; 5,514,774, each incorporated herein by reference.
[0169] In a third aspect additional uses for α-conotoxins are described in U.S. Ser. No. 09/219,446, filed 22 Dec. 1998, incorporated herein by reference. In this application, α-conotoxins with specificity for neuronal nicotinic acetylcholine receptors are used for treating disorders regulated at neuronal nicotinic acetylcholine receptors. Such disorders include, but are not limited to, cardiovascular disorders, gastric motility disorders, urinary incontinence, nicotine addiction, mood disorders (such as bipolar disorder, unipolar depression, dysthymia and seasonal effective disorder) and small cell lung carcinoma, as well as the localization of small cell lung carcinoma.
[0170] The α-conotoxin peptides described herein are sufficiently small to be chemically synthesized. General chemical syntheses for preparing the foregoing α-conotoxin peptides are described hereinafter. Various ones of the α-conotoxin peptides can also be obtained by isolation and purification from specific Conus species using the technique described in U.S. Pat. No. 4,447,356 (Olivera et al., 1984), the disclosure of which is incorporated herein by reference.
[0171] Although the α-conotoxin peptides of the present invention can be obtained by purification from cone snails, because the amounts of α-conotoxin peptides obtainable from individual snails are very small, the desired substantially pure α-conotoxin peptides are best practically obtained in commercially valuable amounts by chemical synthesis using solid-phase strategy. For example, the yield from a single cone snail may be about 10 micrograms or less of α-conotoxin peptide. By "substantially pure" is meant that the peptide is present in the substantial absence of other biological molecules of the same type; it is preferably present in an amount of at least about 85% purity and preferably at least about 95% purity. Chemical synthesis of biologically active α-conotoxin peptides depends of course upon correct determination of the amino acid sequence.
[0172] The α-conotoxin peptides can also be produced by recombinant DNA techniques well known in the art. Such techniques are described by Sambrook et al. (1989). The peptides produced in this manner are isolated, reduced if necessary, and oxidized to form the correct disulfide bonds.
[0173] One method of forming disulfide bonds in the conantokin peptides of the present invention is the air oxidation of the linear peptides for prolonged periods under cold room temperatures or at room temperature. This procedure results in the creation of a substantial amount of the bioactive, disulfide-linked peptides. The oxidized peptides are fractionated using reverse-phase high performance liquid chromatography (HPLC) or the like, to separate peptides having different linked configurations. Thereafter, either by comparing these fractions with the elution of the native material or by using a simple assay, the particular fraction having the correct linkage for maximum biological potency is easily determined. However, because of the dilution resulting from the presence of other fractions of less biopotency, a somewhat higher dosage may be required.
[0174] The peptides are synthesized by a suitable method, such as by exclusively solid-phase techniques, by partial solid-phase techniques, by fragment condensation or by classical solution couplings.
[0175] In conventional solution phase peptide synthesis, the peptide chain can be prepared by a series of coupling reactions in which constituent amino acids are added to the growing peptide chain in the desired sequence. Use of various coupling reagents, e.g., dicyclohexylcarbodiimide or diisopropylcarbonyldimidazole, various active esters, e.g., esters of N-hydroxyphthalimide or N-hydroxy-succinimide, and the various cleavage reagents, to carry out reaction in solution, with subsequent isolation and purification of intermediates, is well known classical peptide methodology. Classical solution synthesis is described in detail in the treatise, "Methoden der Organischen Chemie (Houben-Weyl): Synthese von Peptiden," (1974). Techniques of exclusively solid-phase synthesis are set forth in the textbook, "Solid-Phase Peptide Synthesis," (Stewart and Young, 1969), and are exemplified by the disclosure of U.S. Pat. No. 4,105,603 (Vale et al., 1978). The fragment condensation method of synthesis is exemplified in U.S. Pat. No. 3,972,859 (1976). Other available syntheses are exemplified by U.S. Pat. No. 3,842,067 (1974) and U.S. Pat. No. 3,862,925 (1975). The synthesis of peptides containing γ-carboxyglutamic acid residues is exemplified by Rivier et al. (1987), Nishiuchi et al. (1993) and Zhou et al. (1996).
[0176] Common to such chemical syntheses is the protection of the labile side chain groups of the various amino acid moieties with suitable protecting groups which will prevent a chemical reaction from occurring at that site until the group is ultimately removed. Usually also common is the protection of an α-amino group on an amino acid or a fragment while that entity reacts at the carboxyl group, followed by the selective removal of the α-amino protecting group to allow subsequent reaction to take place at that location. Accordingly, it is common that, as a step in such a synthesis, an intermediate compound is produced which includes each of the amino acid residues located in its desired sequence in the peptide chain with appropriate side-chain protecting groups linked to various ones of the residues having labile side chains.
[0177] As far as the selection of a side chain amino protecting group is concerned, generally one is chosen which is not removed during deprotection of the α-amino groups during the synthesis. However, for some amino acids, e.g., His, protection is not generally necessary. In selecting a particular side chain protecting group to be used in the synthesis of the peptides, the following general rules are followed: (a) the protecting group preferably retains its protecting properties and is not split off under coupling conditions, (b) the protecting group should be stable under the reaction conditions selected for removing the α-amino protecting group at each step of the synthesis, and (c) the side chain protecting group must be removable, upon the completion of the synthesis containing the desired amino acid sequence, under reaction conditions that will not undesirably alter the peptide chain.
[0178] It should be possible to prepare many, or even all, of these peptides using recombinant DNA technology. However, when peptides are not so prepared, they are preferably prepared using the Merrifield solid-phase synthesis, although other equivalent chemical syntheses known in the art can also be used as previously mentioned. Solid-phase synthesis is commenced from the C-terminus of the peptide by coupling a protected α-amino acid to a suitable resin. Such a starting material can be prepared by attaching an α-amino-protected amino acid by an ester linkage to a chloromethylated resin or a hydroxymethyl resin, or by an amide bond to a benzhydrylamine (BHA) resin or paramethylbenzhydrylamine (MBHA) resin. Preparation of the hydroxymethyl resin is described by Bodansky et al. (1966). Chloromethylated resins are commercially available from Bio Rad Laboratories (Richmond, Calif.) and from Lab. Systems, Inc. The preparation of such a resin is described by Stewart and Young (1969). BHA and MBHA resin supports are commercially available, and are generally used when the desired polypeptide being synthesized has an unsubstituted amide at the C-terminus Thus, solid resin supports may be any of those known in the art, such as one having the formulae --O--CH2-resin support, --NH BHA resin support, or --NH-MBHA resin support. When the unsubstituted amide is desired, use of a BHA or MBHA resin is preferred, because cleavage directly gives the amide. In case the N-methyl amide is desired, it can be generated from an N-methyl BHA resin. Should other substituted amides be desired, the teaching of U.S. Pat. No. 4,569,967 (Kornreich et al., 1986) can be used, or should still other groups than the free acid be desired at the C-terminus, it may be preferable to synthesize the peptide using classical methods as set forth in the Houben-Weyl text (1974).
[0179] The C-terminal amino acid, protected by Boc or Fmoc and by a side-chain protecting group, if appropriate, can be first coupled to a chloromethylated resin according to the procedure set forth in K. Horiki et al. (1978), using KF in DMF at about 60° C. for 24 hours with stirring, when a peptide having free acid at the C-terminus is to be synthesized. Following the coupling of the BOC-protected amino acid to the resin support, the α-amino protecting group is removed, as by using trifluoroacetic acid (TFA) in methylene chloride or TFA alone. The deprotection is carried out at a temperature between about 0° C. and room temperature. Other standard cleaving reagents, such as HCl in dioxane, and conditions for removal of specific α-amino protecting groups may be used as described in Schroder & Lubke (1965).
[0180] After removal of the α-amino-protecting group, the remaining α-amino- and side chain-protected amino acids are coupled step-wise in the desired order to obtain the intermediate compound defined hereinbefore, or as an alternative to adding each amino acid separately in the synthesis, some of them may be coupled to one another prior to addition to the solid phase reactor. Selection of an appropriate coupling reagent is within the skill of the art. Particularly suitable as a coupling reagent is N,N'-dicyclohexylcarbodiimide (DCC, DIC, HBTU, HATU, TBTU in the presence of HoBt or HoAt).
[0181] The activating reagents used in the solid phase synthesis of the peptides are well known in the peptide art. Examples of suitable activating reagents are carbodiimides, such as N,N'-diisopropylcarbodiimide and N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide. Other activating reagents and their use in peptide coupling are described by Schroder & Lubke (1965) and Kapoor (1970).
[0182] Each protected amino acid or amino acid sequence is introduced into the solid-phase reactor in about a twofold or more excess, and the coupling may be carried out in a medium of dimethylformamide (DMF):CH2Cl2 (1:1) or in DMF or CH2Cl2 alone. In cases where intermediate coupling occurs, the coupling procedure is repeated before removal of the α-amino protecting group prior to the coupling of the next amino acid. The success of the coupling reaction at each stage of the synthesis, if performed manually, is preferably monitored by the ninhydrin reaction, as described by Kaiser et al. (1970). Coupling reactions can be performed automatically, as on a Beckman 990 automatic synthesizer, using a program such as that reported in Rivier et al. (1978).
[0183] After the desired amino acid sequence has been completed, the intermediate peptide can be removed from the resin support by treatment with a reagent, such as liquid hydrogen fluoride or TFA (if using Fmoc chemistry), which not only cleaves the peptide from the resin but also cleaves all remaining side chain protecting groups and also the α-amino protecting group at the N-terminus if it was not previously removed to obtain the peptide in the form of the free acid. If Met is present in the sequence, the Boc protecting group is preferably first removed using trifluoroacetic acid (TFA)/ethanedithiol prior to cleaving the peptide from the resin with HF to eliminate potential S-alkylation. When using hydrogen fluoride or TFA for cleaving, one or more scavengers such as anisole, cresol, dimethyl sulfide and methylethyl sulfide are included in the reaction vessel.
[0184] Cyclization of the linear peptide is preferably affected, as opposed to cyclizing the peptide while a part of the peptido-resin, to create bonds between Cys residues. To effect such a disulfide cyclizing linkage, fully protected peptide can be cleaved from a hydroxymethylated resin or a chloromethylated resin support by ammonolysis, as is well known in the art, to yield the fully protected amide intermediate, which is thereafter suitably cyclized and deprotected. Alternatively, deprotection, as well as cleavage of the peptide from the above resins or a benzhydrylamine (BHA) resin or a methylbenzhydrylamine (MBHA), can take place at 0° C. with hydrofluoric acid (HF) or TFA, followed by oxidation as described above.
[0185] The peptides are also synthesized using an automatic synthesizer. Amino acids are sequentially coupled to an MBHA Rink resin (typically 100 mg of resin) beginning at the C-terminus using an Advanced Chemtech 357 Automatic Peptide Synthesizer. Couplings are carried out using 1,3-diisopropylcarbodimide in N-methylpyrrolidinone (NMP) or by 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) and diethyliso-propylethylamine (DIEA). The FMOC protecting group is removed by treatment with a 20% solution of piperidine in dimethylformamide(DMF). Resins are subsequently washed with DMF (twice), followed by methanol and NMP.
[0186] Pharmaceutical compositions containing a compound of the present invention or its pharmaceutically acceptable salts as the active ingredient can be prepared according to conventional pharmaceutical compounding techniques. See, for example, Remington's Pharmaceutical Sciences, 18th Ed. (1990, Mack Publishing Co., Easton, Pa.). Typically, an antagonistic amount of the active ingredient will be admixed with a pharmaceutically acceptable carrier. The carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g., intravenous, oral or parenteral. The compositions may further contain antioxidizing agents, stabilizing agents, preservatives and the like.
[0187] For oral administration, the compounds can be formulated into solid or liquid preparations such as capsules, pills, tablets, lozenges, melts, powders, suspensions or emulsions. In preparing the compositions in oral dosage form, any of the usual pharmaceutical media may be employed, such as, for example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents, suspending agents, and the like in the case of oral liquid preparations (such as, for example, suspensions, elixirs and solutions); or carriers such as starches, sugars, diluents, granulating agents, lubricants, binders, disintegrating agents and the like in the case of oral solid preparations (such as, for example, powders, capsules and tablets). Because of their ease in administration, tablets and capsules represent the most advantageous oral dosage unit form, in which case solid pharmaceutical carriers are obviously employed. If desired, tablets may be sugar-coated or enteric-coated by standard techniques. The active agent can be encapsulated to make it stable to passage through the gastrointestinal tract while at the same time allowing for passage across the blood brain barrier. See for example, WO 96/11698.
[0188] For parenteral administration, the compound may be dissolved in a pharmaceutical carrier and administered as either a solution or a suspension. Illustrative of suitable carriers are water, saline, dextrose solutions, fructose solutions, ethanol, or oils of animal, vegetative or synthetic origin. The carrier may also contain other ingredients, for example, preservatives, suspending agents, solubilizing agents, buffers and the like. When the compounds are being administered intrathecally, they may also be dissolved in cerebrospinal fluid.
[0189] The active agent is preferably administered in an therapeutically effective amount. The actual amount administered, and the rate and time-course of administration, will depend on the nature and severity of the condition being treated. Prescription of treatment, e.g. decisions on dosage, timing, etc., is within the responsibility of general practitioners or specialists, and typically takes account of the disorder to be treated, the condition of the individual patient, the site of delivery, the method of administration and other factors known to practitioners. Examples of techniques and protocols can be found in Remington's Pharmaceutical Sciences. Typically the conopeptides of the present invention exhibit their effect at a dosage range from about 0.001 mg/kg to about 250 mg/kg, preferably from about 0.05 mg/kg to about 100 mg/kg of the active ingredient, more preferably from a bout 0.1 mg/kg to about 75 mg/kg. A suitable dose can be administered in multiple sub-doses per day. Typically, a dose or sub-dose may contain from about 0.1 mg to about 500 mg of the active ingredient per unit dosage form. A more preferred dosage will contain from about 0.5 mg to about 100 mg of active ingredient per unit dosage form. Dosages are generally initiated at lower levels and increased until desired effects are achieved.
[0190] Alternatively, targeting therapies may be used to deliver the active agent more specifically to certain types of cell, by the use of targeting systems such as antibodies or cell specific ligands. Targeting may be desirable for a variety of reasons, e.g. if the agent is unacceptably toxic, or if it would otherwise require too high a dosage, or if it would not otherwise be able to enter the target cells.
[0191] The active agents, which are peptides, can also be administered in a cell based delivery system in which a DNA sequence encoding an active agent is introduced into cells designed for implantation in the body of the patient, especially in the spinal cord region. Suitable delivery systems are described in U.S. Pat. No. 5,550,050 and published PCT Application Nos. WO 92/19195, WO 94/25503, WO 95/01203, WO 95/05452, WO 96/02286, WO 96/02646, WO 96/40871, WO 96/40959 and WO 97/12635. Suitable DNA sequences can be prepared synthetically for each active agent on the basis of the developed sequences and the known genetic code.
EXAMPLES
[0192] The present invention is described by reference to the following Examples, which are offered by way of illustration and are not intended to limit the invention in any manner. Standard techniques well known in the art or the techniques specifically described below were utilized.
Example 1
Isolation of α-Conotoxins
[0193] Crude venom was extracted from venom ducts (Cruz et al., 1976), and the components were purified as previously described (Cartier et al., 1996a). The crude extract from venom ducts was purified by reverse phase liquid chromatography (RPLC) using a Vydac C18 semi-preparative column (10×250 mm) and elution with a linear gradient of acetonitrile in 0.1% TFA. Further purification of bioactive peaks was done on a Vydac C18 analytical column (4.6×220 mm) eluted with a gradient of acetonitrile in 0.1% TFA. The effluents were monitored at 220 nm. Peaks were collected, and aliquots were assayed for activity. Activity was monitored by assessing block of α3β4 nAChRs expressed in Xenopus oocytes.
[0194] The amino acid sequence of the purified peptides were determined by standard methods. The purified peptides were reduced and alkylated prior to sequencing by automated Edman degradation on an Applied Biosystems 477A Protein Sequencer with a 120A Analyzer (DNA/Peptide Facility, University of Utah) (Martinez et al., 1995; Shon et al., 1994).
[0195] In accordance with this method, peptides MII, AuIA, AuIB, AuIC, MAR-1, MAR-2, TI, OB-29, EpI, S1.1, Bn1.1, Bn1.2, Ca1.1, Ca1.2, Cn1.1, Cn1.2 and Sm1.3 were obtained.
Example 2
Synthesis of Conopeptides
[0196] The synthesis of conopeptides, either the mature toxins or the precursor peptides, was separately performed using conventional protection chemistry as described by Cartier et al. (1996). Briefly, the linear chains were built on Rink amide resin by Fmoc procedures with 2-(1H-benzotriol-1-yl)-1,1,3,3,-tetramethyluronium tetrafluoroborated coupling using an ABI model 430A peptide synthesizer with amino acid derivatives purchased from Bachem (Torrance Calif.). Orthogonal protection was used on cysteines: Cys3 and Cys16 were protected as the stable Cys(S-acetamidomethyl), while Cys2 and Cys8 were protected as the acid-labile Cys(S-trityl). After removal of the terminal Fmoc protecting group and cleavage of the peptides from the resins, the released peptides were precipitated by filtering the reaction mixture into -10° C. methyl t-butyl ether, which removed the protecting groups except on Cys3 and Cys16. The peptides were dissolved in 0.1% TFA and 60% acetonitrile and purified by RPLC on a Vydac C18 preparative column (22×250 mm) and eluted at a flow rate of 20 mL/min with a gradient of acetonitrile in 0.1% TFA.
[0197] The disulfide bridges in the three conopeptides were formed as described in Cartier et al. (1996). Briefly, the disulfide bridges between Cys2 and Cys8 were formed by air oxidation which was judged to be complete by analytical RPLC. The monocyclic peptides were purified by RPLC on a Vydac C18 preparative column (22×250 mm) and eluted with a gradient of acetonitrile in 0.1% TFA. Removal of S-acetamidomethyl groups and closure of the disulfide bridge between Cys3 and Cys16 was carried out simultaneously be iodine oxidation. The cyclic peptides were purified by RPLC on a Vydac C18 preparative column (22×250 mm) and eluted with a gradient of acetonitrile in 0.1% TFA.
Example 3
Isolation of DNA Encoding α-Conotoxins
[0198] DNA coding for α-conotoxins was isolated and cloned in accordance with conventional techniques using general procedures well known in the art, such as described in Olivera et al. (1996). Alternatively, cDNA libraries was prepared from Conus venom duct using conventional techniques. DNA from single clones was amplified by conventional techniques using primers which correspond approximately to the M13 universal priming site and the M13 reverse universal priming site. Clones having a size of approximately 300 nucleotides were sequenced and screened for similarity in sequence to known α-conotoxins. The DNA sequences and encoded propeptide or peptide sequences are set forth in Tables 1-134.
TABLE-US-00005 TABLE 1 DNA Sequence (SEQ ID NO: 58) and Protein Sequence (SEQ ID NO: 59) of MII atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc cct tca gat cgt gca tct gat ggc agg aat gcc gca gcc aac gac Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp aaa gcg tct gac gtg atc acg ctg gcc ctc aag gga tgc tgt tcc aac Lys Ala Ser Asp Val Ile Thr Leu Ala Leu Lys Gly Cys Cys Ser Asn cct gtc tgt cac ttg gag cat tca aac ctt tgt ggt aga aga cgc Pro Val Cys His Leu Glu His Ser Asn Leu Cys Gly Arg Arg Arg tgatgctcca ggaccctctg aaccacgacg ttcgagca
TABLE-US-00006 TABLE 2 DNA Sequence (SEQ ID NO: 60) and Protein Sequence (SEQ ID NO: 61) of AuIA atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca gat cgt gca tct gat ggc agg aag gac gca gcg tct ggc Phe Thr Ser Asp Arg Ala Ser Asp Gly Arg Lys Asp Ala Ala Ser Gly ctg atc gct ctg acc atc aag gga tgc tgt tct tat cct ccc tgt ttc Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser Tyr Pro Pro Cys Phe gcg act aat tca gac tat tgt ggt tgacgacgct gatgctccag gaccctctga Ala Thr Asn Ser Asp Tyr Cys Gly accacgacgt
TABLE-US-00007 TABLE 3 DNA Sequence (SEQ ID NO: 62) and Protein Sequence (SEQ ID NO: 63) of AuIB atg ttc acc gtg ttt ctg ttg gtc gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca gat cgt gca tct gat ggc agg aag gac gca gcg tct ggc Phe Thr Ser Asp Arg Ala Ser Asp Gly Arg Lys Asp Ala Ala Ser Gly ctg att gct ctg acc atg aag gga tgc tgt tct tat cct ccc tgt ttc Leu Ile Ala Leu Thr Met Lys Gly Cys Cys Ser Tyr Pro Pro Cys Phe gcg act aat cca gac tgt ggt cga cga cgc tgatgctcca ggaccctctg Ala Thr Asn Pro Asp Cys Gly Arg Arg Arg aaccacgacg t
TABLE-US-00008 TABLE 4 DNA Sequence (SEQ ID NO: 64) and Protein Sequence (SEQ ID NO: 65) of Tx1.3 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc tct tca ggt cgt agt aca ttt cgt ggc agg aat gcc gca gcc aaa Phe Ser Ser Gly Arg Ser Thr Phe Arg Gly Arg Asn Ala Ala Ala Lys gcg tct ggc ctg gtc agt ctg act gac agg aga cca gaa tgc tgt agt Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Glu Cys Cys Ser gat cct cgc tgt aac tcg agt cat cca gaa ctt tgt ggt gga aga cgc Asp Pro Arg Cys Asn Ser Ser His Pro Glu Leu Cys Gly Gly Arg Arg tgatgctcca ggaccctctg aaccacgacg t
TABLE-US-00009 TABLE 5 DNA Sequence (SEQ ID NO: 66) and Protein Sequence (SEQ ID NO: 67) of Tx1.2 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc gcc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Ala Val Val Ser ttc act tca gat cgt gca tct gat gac ggg aaa gcc gct gcg tct gac Phe Thr Ser Asp Arg Ala Ser Asp Asp Gly Lys Ala Ala Ala Ser Asp ctg atc act ctg acc atc aag gga tgc tgt tct cgt cct ccc tgt atc Leu Ile Thr Leu Thr Ile Lys Gly Cys Cys Ser Arg Pro Pro Cys Ile gcg aat aat cca gac ttg tgt ggt tgacgacgct gatgctccag aacggtctga Ala Asn Asn Pro Asp Leu Cys Gly accacgacgt tcgagcaatg ttcaccgtgt ttctgttggt tgtctt
TABLE-US-00010 TABLE 6 DNA Sequence (SEQ ID NO: 68) and Protein Sequence (SEQ ID NO: 69) of Tx1.1 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca ggt cgt agt aca ttt cgt ggc agg aat gcc gca gcc aaa Phe Thr Ser Gly Arg Ser Thr Phe Arg Gly Arg Asn Ala Ala Ala Lys gcg tct ggc ctg gtc agt ctg act gac agg aga cca caa tgc tgt tct Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Gln Cys Cys Ser cat cct gcc tgt aac gta gat cat cca gaa att tgt cgt tgaagacgct His Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Arg gatgctccag gaccctctga accacgacgt
TABLE-US-00011 TABLE 7 DNA Sequence (SEQ ID NO: 70) and Protein Sequence (SEQ ID NO: 71) of R1.1A atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca ggt cgt cgt aca ttt cat ggc agg aat gcc gca gcc aaa Phe Thr Ser Gly Arg Arg Thr Phe His Gly Arg Asn Ala Ala Ala Lys gcg tct ggc ctg gtc agt ctg act gac agg aga cca gaa tgc tgt tct Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Glu Cys Cys Ser cat cct gcc tgt aac gta gat cat cca gaa att tgt cgt tgaagacgct His Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Arg gatgctccag gaccctctga accacgacgt
TABLE-US-00012 TABLE 8 DNA Sequence (SEQ ID NO: 72) and Protein Sequence (SEQ ID NO: 73) of R1.1B atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca ggt cgt agt aca ttt cgt ggc agg aat gcc gca gcc aaa Phe Thr Ser Gly Arg Ser Thr Phe Arg Gly Arg Asn Ala Ala Ala Lys gcg tct ggc ctg gtc agt ctg act gac agg aga cca caa tgc tgt tct Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Gln Cys Cys Ser cat cct gcc tgt aac gta gat cat cca gaa att tgc gat tgaagacgct His Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Asp gatgctccag gaccctctga accacgacgt
TABLE-US-00013 TABLE 9 DNA Sequence (SEQ ID NO: 74) and Protein Sequence (SEQ ID NO: 75) of S1.1 atg ttc act gtg ttt ctg ttg gtt gtc ttg gca atc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Ile Thr Val Val Ser ttc cct tta gat cgt gaa tct gat ggc gcg aat gcc gaa gcc cgc acc Phe Pro Leu Asp Arg Glu Ser Asp Gly Ala Asn Ala Glu Ala Arg Thr cac gat cat gag aag cac gca ctg gac cgg aat gga tgc tgt agg aat His Asp His Glu Lys His Ala Leu Asp Arg Asn Gly Cys Cys Arg Asn cct gcc tgt gag agc cac aga tgt ggt tgacgacgct gatgctccag Pro Ala Cys Glu Ser His Arg Cys Gly gaccctctga accacgacgt tcgagca
TABLE-US-00014 TABLE 10 DNA Sequence (SEQ ID NO: 76) and Protein Sequence (SEQ ID NO: 77) of Bn1.1 atg ttc acc atg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Met Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc gct tca gat cgt gca tct gat ggc agg aat gcc gca gcc aag gac Phe Ala Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Lys Asp aaa gcg tct gac ctg gtc gct ctg acc gtc aag gga tgc tgt tct cat Lys Ala Ser Asp Leu Val Ala Leu Thr Val Lys Gly Cys Cys Ser His cct gcc tgt agc gtg aat aat cca gac att tgt ggt tgaagacgct Pro Ala Cys Ser Val Asn Asn Pro Asp Ile Cys Gly gatgctccag gaccctctga accacgacgt tcgagca
TABLE-US-00015 TABLE 11 DNA Sequence (SEQ ID NO: 78) and Protein Sequence (SEQ ID NO: 79) of Bn1.2 aaa gaa tgc tgt act cat cct gcc tgt cac gtg agt cat cca gaa ctc Lys Glu Cys Cys Thr His Pro Ala Cys His Val Ser His Pro Glu Leu tgt ggt tgaaaagcga cgtgacgctc caggaccctc tgaaccacga cgttcgagca Cys Gly
TABLE-US-00016 TABLE 12 DNA Sequence (SEQ ID NO: 80) and Protein Sequence (SEQ ID NO: 81) of Bn1.3 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca act gct gtt ctt cca Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Ala Val Leu Pro gtc act tta gat cgt gca tct gat gga agg aat gca gca gcc aac gcc Val Thr Leu Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala aaa acg cct cgc ctg atc gcg cca ttc atc agg gat tat tgc tgt cat Lys Thr Pro Arg Leu Ile Ala Pro Phe Ile Arg Asp Tyr CysC ys His aga ggt ccc tgt atg gta tgg tgt ggt tgaagccgct gctgctccag Arg Gly Pro Cys Met Val Trp Cys Gly gaccctctga accac
TABLE-US-00017 TABLE 13 DNA Sequence (SEQ ID NO: 82) and Protein Sequence (SEQ ID NO: 83) of Ca1.1 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtg gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca gat cgt gct tct gat ggc agg aat gcc gca gcc aac gcg Phe Thr Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala ttt gac ctg atc gct ctg atc gcc agg caa aat tgc tgt agc att ccc Phe Asp Leu Ile Ala Leu Ile Ala Arg Gln Asn Cys Cys Ser Ile Pro agc tgt tgg gag aaa tat aaa tgt agt taa Ser Cys Trp Glu Lys Tyr Lys Cys Ser
TABLE-US-00018 TABLE 14 DNA Sequence (SEQ ID NO: 84) and Protein Sequence (SEQ ID NO: 85) of Ca1.2 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtg gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca gat cgt gcg tct gaa ggc agg aat gct gca gcc aag gac Phe Thr Ser Asp Arg Ala Ser Glu Gly Arg Asn Ala Ala Ala Lys Asp aaa gcg tct gac ctg gtg gct ctg aca gtc agg gga tgc tgt gcc att Lys Ala Ser Asp Leu Val Ala Leu Thr Val Arg Gly Cys Cys Ala Ile cgt gaa tgt cgc ttg cag aat gca gcg tat tgt ggt gga ata tac Arg Glu Cys Arg Leu Gln Asn Ala Ala Tyr Cys Gly Gly Ile Tyr tgatgctcca ggaccctctg aaccacgacg
TABLE-US-00019 TABLE 15 DNA Sequence (SEQ ID NO: 86) and Protein Sequence (SEQ ID NO: 87) of TIB atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc cct tca gat att gca act gag ggc agg aat gcc gca gcc aaa gcg Phe Pro Ser Asp Ile Ala Thr Glu Gly Arg Asn Ala Ala Ala Lys Ala ttt gac ctg ata tct tcg atc gtc aag aaa gga tgc tgt tcc cat cct Phe Asp Leu Ile Ser Ser Ile Val Lys Lys Gly Cys Cys Ser His Pro gcc tgt tcg ggg aat aat cca gaa ttt tgt cgt caa ggt cgc Ala Cys Ser Gly Asn Asn Pro Glu Phe Cys Arg Gln Gly Arg tgatgctcca ggaccctctg aaccacgacg t
TABLE-US-00020 TABLE 16 DNA Sequence (SEQ ID NO: 88) and Protein Sequence (SEQ ID NO: 89) of TIA atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc cct tca gat ata gca act gag ggc agg aat gcc gca gcc aaa gcg Phe Pro Ser Asp Ile Ala Thr Glu Gly Arg Asn Ala Ala Ala Lys Ala ttt gac ctg ata tct tcg atc gtc agg aaa gga tgc tgt tcc aat ccc Phe Asp Leu Ile Ser Ser Ile Val Arg Lys Gly Cys Cys Ser Asn Pro gcc tgt gcg ggg aat aat cca cat gtt tgt cgt caa ggt cgc Ala Cys Ala Gly Asn Asn Pro His Val Cys Arg Gln Gly Arg tgatgctcca ggaccctctg aaccacgacg t
TABLE-US-00021 TABLE 17 DNA Sequence (SEQ ID NO: 90) and Protein Sequence (SEQ ID NO: 91) of S11.1 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc aat tca gat cgt gat cca gca tta ggt ggc agg aat gct gca gcc Phe Asn Ser Asp Arg Asp Pro Ala Leu Gly Gly Arg Asn Ala Ala Ala aaa gcg tct gac aag atc gct tcg acc ctc aag aga aga gga tgc tgt Lys Ala Ser Asp Lys Ile Ala Ser Thr Leu Lys Arg Arg Gly Cys Cys tcg tat ttt gac tgt aga atg atg ttt cca gaa atg tgt ggt tgg cga Ser Tyr Phe Asp Cys Arg Met Met Phe Pro Glu Met Cys Gly Trp Arg ggc tgatgctcca ggaccctctg aaccacgacg t Gly
TABLE-US-00022 TABLE 18 DNA Sequence (SEQ ID NO: 92) and Protein Sequence (SEQ ID NO: 93) of S11.2 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc aat tca gat cgt gat cca gca tta ggt ggc agg aat gct gca gcc Phe Asn Ser Asp Arg Asp Pro Ala Leu Gly Gly Arg Asn Ala Ala Ala ata gcg tct gac aag atc gct tcg acc ctc agg aga gga gga tgc tgt Ile Ala Ser Asp Lys Ile Ala Ser Thr Leu Arg Arg Gly Gly Cys Cys tct ttt cct gcc tgt aga aag tat cgt cca gaa atg tgt ggt gga cga Ser Phe Pro Ala Cys Arg Lys Tyr Arg Pro Glu Met Cys Gly Gly Arg cgc tgatgctcca ggaccctctg aaccacgacg t Arg
TABLE-US-00023 TABLE 19 DNA Sequence (SEQ ID NO: 94) and Protein Sequence (SEQ ID NO: 95) of S11.3 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca gat cat gaa tct gat cgc ggt gat gcc caa acc atc caa Phe Thr Ser Asp His Glu Ser Asp Arg Gly Asp Ala Gln Thr Ile Gln gaa gtg ttt gag atg ttc gct ctg gac agc gat gga tgc tgt tgg cat Glu Val Phe Glu Met Phe Ala Leu Asp Ser Asp Gly Cys Cys Trp His cct gct tgt ggc aga cac tat tgt ggt cga aga cgc tgatgctcca Pro Ala Cys Gly Arg His Tyr Cys Gly Arg Arg Arg ggaccctctg aaccacgacg t
TABLE-US-00024 TABLE 20 DNA Sequence (SEQ ID NO: 96) and Protein Sequence (SEQ ID NO: 97) of S11.6 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc aat tca gat cgt gat cca gca tta ggt ggc agg aat gct gca gcc Phe Asn Ser Asp Arg Asp Pro Ala Leu Gly Gly Arg Asn Ala Ala Ala ata gcg tct gac aag atc gct tcg acc ctc agg aga gga gga tgc tgt Ile Ala Ser Asp Lys Ile Ala Ser Thr Leu Arg Arg Gly Gly Cys Cys tct ttt gct gcc tgt aga aag tat cgt cca gaa atg tgt ggt gga cga Ser Phe Ala Ala Cys Arg Lys Tyr Arg Pro Glu Met Cys Gly Gly Arg cgc tgatgct Arg
TABLE-US-00025 TABLE 21 DNA Sequence (SEQ ID NO: 98) and Protein Sequence (SEQ ID NO: 99) of S11.7 atg ttc acc gtg ttt ctg ttg gtt ctc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Leu Leu Ala Thr Thr Val Val Ser ttc aat tca gat cgt gca tta ggt ggc agg aat gct gca gcc aaa gcg Phe Asn Ser Asp Arg Ala Leu Gly Gly Arg Asn Ala Ala Ala Lys Ala tct gac aag atc ctt tcg aac ctc agg aga gga gga tgc tgt ttt cat Ser Asp Lys Ile Leu Ser Asn Leu Arg Arg Gly Gly Cys Cys Phe His cct gtc tgt tac atc aat ctt cta gaa atg tgt cgt caa cga ggc Pro Val Cys Tyr Ile Asn Leu Leu Glu Met Cys Arg Gln Arg Gly tgatcgtcca ggaccctctg aaccacgacg t
TABLE-US-00026 TABLE 22 DNA Sequence (SEQ ID NO: 100) and Protein Sequence (SEQ ID NO: 101) of Cn1.1 atg ttc acc gtg ttt ctg ttg gtt gtc ttg aca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Thr Thr Thr Val Val Ser ttc cct tca gat agt gca tct gat gtc agg gat gac gaa gcc aaa gac Phe Pro Ser Asp Ser Ala Ser Asp Val Arg Asp Asp Glu Ala Lys Asp gaa agg tct gac atg tac aaa tcg aaa cgg aat gga cgc tgt tgc cat Glu Arg Ser Asp Met Tyr Lys Ser Lys Arg Asn Gly Arg Cys Cys His cct gcc tgt ggc aaa cac ttt agt tgt gga cgc tgatgctcca ggaccctctg Pro Ala Cys Gly Lys His Phe Ser Cys Gly Arg aaccacgacg t
TABLE-US-00027 TABLE 23 DNA Sequence (SEQ ID NO: 102) and Protein Sequence (SEQ ID NO: 103) of SmI atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser tcc cct tca gat cgt gca tct gat ggc agg aat gcc gca gcc aac gag Ser Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Glu aaa gcg tct gac gtg atc gcg ctg gcc ctc aag gga tgc tgt tcc aac Lys Ala Ser Asp Val Ile Ala Leu Ala Leu Lys Gly Cys Cys Ser Asn cct gtc tgt cac ctg gag cat tca aac atg tgt ggt aga aga cgc Pro Val Cys His Leu Glu His Ser Asn Met Cys Gly Arg Arg Arg tgatgctcca ggaccctctg aaccacgacg
TABLE-US-00028 TABLE 24 DNA Sequence (SEQ ID NO: 104) and Protein Sequence (SEQ ID NO: 105) of Bt1.1 atg ttc tcc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Ser Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser tcc act tca ggt ggt gca tct ggt ggc agg aag gct gca gcc aaa gcg Ser Thr Ser Gly Gly Al aSer Gly Gly Arg Lys Ala Ala Ala Lys Ala tct aac cgg atc gct ctg acc gtc agg agt gca aca tgc tgt aat tat Ser Asn Arg Ile Ala Leu Thr Val Arg Ser Ala Thr Cys Cys Asn Tyr cct ccc tgt tac gag act tat cca gaa agt tgt ctg taacgtgaat Pro Pro Cys Tyr Glu Thr Tyr Pro Glu Ser Cys Leu catccagagc tttgtggctg aagacactga tgctccagga ccctctgaac cacgacgt
TABLE-US-00029 TABLE 25 DNA Sequence (SEQ ID NO: 106) and Protein Sequence (SEQ ID NO: 107) of Bt1.2 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtg gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca ggt cgt gca ttt cgt ggc agg aat cgc gca gcc gac gac Phe Thr Ser Gly Arg Ala Phe Arg Gly Arg Asn Arg Ala Ala Asp Asp aaa agg tct gac ctg gcc gct ctg agc gtc agg gga gga tgc tgt tcc Lys Arg Ser Asp Leu Ala Ala Leu Ser Val Arg Gly Gly Cys Cys Ser cat cct gcc tgt gcg gtg aat cat cca gag ctt tgt ggc tgaagacgct His Pro Ala Cys Ala Val Asn His Pro Glu Leu Cys Gly gatgccccag gaccctctga accacgacgt
TABLE-US-00030 TABLE 26 DNA Sequence (SEQ ID NO: 108) and Protein Sequence (SEQ ID NO: 109) of Bt1.3 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca ggt cgt gca tct ggt ggc agg aat gct gca gcc aaa gcg Phe Thr Ser Gly Arg Ala Ser Gly Gly Arg Asn Ala Ala Ala Lys Ala tct aac cgg atc gct atg gcc atc agc agt gga gca tgc tgt gca tat Ser Asn Arg Ile Ala Met Ala Ile Ser Ser Gly Ala Cys Cys Ala Tyr cct ccc tgt ttc gag gct tat cca gaa aga tgt ctg taacgtgaat Pro Pro Cys Phe Glu Ala Tyr Pro Glu Arg Cys Leu catccagacc tttgtggctg aagacgctga tgccccagga ccctctgaac cacgacgt
TABLE-US-00031 TABLE 27 DNA Sequence (SEQ ID NO: 110) and Protein Sequence (SEQ ID NO: 111) of Bt1.4 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca gat cgt gca ttt cgt ggc agg aat tcc gca gcc aac gac Phe Thr Ser Asp Arg Ala Phe Arg Gly Arg Asn Ser Ala Ala Asn Asp aaa agg tct gac ctg gcc gct ctg agc gtc agg aga gga tgc tgc tcc Lys Arg Ser Asp Leu Ala Ala Leu Ser Val Arg Arg Gly Cys Cys Ser cat ccc gcc tgt agc gtg aat cat cca gag ctt tgt ggt aga aga cgc His Pro Ala Cys Ser Val Asn His Pro Glu Leu Cys Gly Arg Arg Arg tgatgcccca ggaccctctg aaccacgacg t
TABLE-US-00032 TABLE 28 DNA Sequence (SEQ ID NO: 112) and Protein Sequence (SEQ ID NO: 113) of Bt1.5 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca ggt cgt gca tct ggt ggc agg aat gct gca gcc aaa gcg Phe Thr Ser Gly Arg Ala Ser Gly Gly Arg Asn Ala Ala Ala Lys Ala tct aac cgg atc gct ctg atc gtc agg aat gca gaa tgc tgt tat tat Ser Asn Arg Ile Ala Leu Ile Val Arg Asn Ala Glu Cys Cys Tyr Tyr cct ccc tgt tac gag gct tat cca gaa att tgt ctg taacgtgaat Pro Pro Cys Tyr Glu Ala Tyr Pro Glu Ile Cys Leu catccagacc tttgtggctg aagaccctga tgctccagga ccctctgaac cacgacgt
TABLE-US-00033 TABLE 29 DNA Sequence (SEQ ID NO: 114) and Protein Sequence (SEQ ID NO: 115) of Pn1.1 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc att tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Ile Ser ttc act tca gat cgt gca tct gat ggc ggg aat gcc gca gcg tct gac Phe Thr Ser Asp Arg Ala Ser Asp Gly Gly Asn Ala Ala Ala Ser Asp ctg atc gct ctg acc atc aag gga tgc tgt tct cat cct ccc tgt gcc Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser His Pro Pro Cys Ala atg aat aat cca gac tat tgt ggt tgacgacgct gatgctccag gaccctctga Met Asn Asn Pro Asp Tyr Cys Gly accacgacg
TABLE-US-00034 TABLE 30 DNA Sequence (SEQ ID NO: 116) and Protein Sequence (SEQ ID NO: 117) of Pn1.2 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca gat cgt gca tct gat ggc ggg aat gcc gca atg tct gac Phe Thr Ser Asp Arg Ala Ser Asp Gly Gly Asn Ala Ala Met Ser Asp ctg atc gct ctg acc atc aag gga tgc tgt tct cat cct ccc tgt ttc Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser His Pro Pro Cys Phe ctg aat aat cca gac tat tgt ggt tgacgacgct gatgctccag gaccctctga Leu Asn Asn Pro Asp Tyr Cys Gly accacgacg
TABLE-US-00035 TABLE 31 DNA Sequence (SEQ ID NO: 118) and Protein Sequence (SEQ ID NO: 119) of Sm1.3 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc cct tca gat cgt gaa tct gat ggc gcg aat gac gaa gcc cgc acc Phe Pro Ser Asp Arg Glu Ser Asp Gly Ala Asn Asp Glu Ala Arg Thr gac gag cct gag gag cac gga ccg gac agg aat gga tgc tgt agg aat Asp Glu Pro Glu Glu His Gly Pro Asp Arg Asn Gly Cys Cys Arg Asn cct gcc tgt gag agc cac aga tgt ggt tgacgacgct gatgctccag Pro Ala Cys Glu Ser His Arg Cys Gly gaccctctga accacgacg
TABLE-US-00036 TABLE 32 DNA Sequence (SEQ ID NO: 120) and Protein Sequence (SEQ ID NO: 121) of Cr1.2 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc cct tca gat cgt gca tct gat ggc agg aat gcc gca gcc agc gac Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Ser Asp aga gcg tct gac gcg gcc cac cag gga tgc tgt tcc aac cct gtc tgt Arg Ala Ser Asp Ala Ala His Gln Gly Cys Cys Ser Asn Pro Val Cys cac gtg gaa cat cca gaa ctt tgt cgt aga aga cgc tgatgctcca His Val Glu His Pro Glu Leu Cys Arg Arg Arg Arg ggaccctctg aaccacgacg
TABLE-US-00037 TABLE 33 DNA Sequence (SEQ ID NO: 122) and Protein Sequence (SEQ ID NO: 123) of Cr1.3 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc cct tca aat cgt gaa tct gat ggc gcg aat gcc gaa gtc cgc acc Phe Pro Ser Asn Arg Glu Ser Asp Gly Ala Asn Ala Glu Val Arg Thr gac gag cct gag gag cac gac gaa ctg ggc ggg aat gga tgc tgt ggg Asp Glu Pro Glu Glu His Asp Glu Leu Gly Gly Asn Gly Cys Cys Gly aat cct gac tgt acg agc cac agt tgt gat tgacgacgct gatgctccag Asn Pro Asp Cys Thr Ser His Ser Cys Asp gaccctctga accacgacg
TABLE-US-00038 TABLE 34 DNA Sequence (SEQ ID NO: 124) and Protein Sequence (SEQ ID NO: 125) of EpI atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca gat cgt gca tct gat agc agg aag gac gca gcg tct ggc Phe Thr Ser Asp Arg Ala Ser Asp Ser Arg Lys Asp Ala Ala Ser Gly ctg atc gct ctg acc atc aag gga tgc tgt tct gat cct cgc tgt aac Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser Asp Pro Arg Cys Asn atg aat aat cca gac tat tgt ggt tgacgacgct gatgctccag gaccctctga Met Asn Asn Pro Asp Tyr Cys Gly accacgacg
TABLE-US-00039 TABLE 35 DNA Sequence (SEQ ID NO: 126) and Protein Sequence (SEQ ID NO: 127) of Sn1.1 atg tcc acc gtg ttt ctg ttg gtt gtc ctc gca acc acc gtc gtt tcc Met Ser Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act gta gat cgt gca tct gat ggc agg gat gtc gca atc gac gac Phe Thr Val Asp Arg Ala Ser Asp Gly Arg Asp Val Ala Ile Asp Asp aga ttg gtg tct ctc cct cag atc gcc cat gct gac tgt tgt tcc gat Arg Leu Val Ser Leu Pro Gln Ile Ala His Ala Asp Cys Cys Ser Asp cct gcc tgc aag cag acg ccc ggt tgt cgt taaagacgct gctgctccag Pro Ala Cys Lys Gln Thr Pro Gly Cys Arg gaccctctga accacgacg
TABLE-US-00040 TABLE 36 DNA Sequence (SEQ ID NO: 128) and Protein Sequence (SEQ ID NO: 129) of Sn1.2 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gct tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Ala Ser ttc att atc gat gat cca tct gat ggc agg aat att gca gtc gac gac Phe Ile Ile Asp Asp Pro Ser Asp Gly Arg Asn Ile Ala Val Asp Asp aga ggg ctt ttc tct acg ctc ttc cat gct gat tgc tgt gaa aat cct Arg Gly Leu Phe Ser Thr Leu Phe His Ala Asp Cys Cys Glu Asn Pro gcc tgt aga cac acg cag ggt tgt tgatctttgt tcttcaaaga cactgctggc Ala Cys Arg His Thr Gln Gly Cys ccaggaccct ctgaaccacg acg
TABLE-US-00041 TABLE 37 DNA Sequence (SEQ ID NO: 130) and Protein Sequence (SEQ ID NO: 131) of Da1.1 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca gat cgt gca ttt cgt ggc agg aat gcc gca gcc aaa gag Phe Thr Ser Asp Arg Ala Phe Arg Gly Arg Asn Ala Ala Ala Lys Glu tct ggc ctg gtc ggt ctg acc gac aag acg cga gga tgc tgt tct cat Ser Gly Leu Val Gly Leu Thr Asp Lys Thr Arg Gly Cys Cys Ser His cct gcc tgt aac gta gat cat cca gaa att tgt ggt tgaagacgct Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Gly gatgctccag gaccctctga accacgacgt
TABLE-US-00042 TABLE 38 DNA Sequence (SEQ ID NO: 132) and Protein Sequence (SEQ ID NO: 133) of Da1.2 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca gat ggt gca tct gat gac agg aaa gcc gct gcg tct gac Phe Thr Ser Asp Gly Ala Ser Asp Asp Arg Lys Ala Ala Ala Ser Asp ctg atc act ctg acc atc aag gga tgc tgt tct cgt cct ccc tgt atc Leu Ile Thr Leu Thr Ile Lys Gly Cys Cys Ser Arg Pro Pro Cys Ile gcg aat aat cca gac ttg tgt ggt cga cga cgc tgatgctcca ggaccctctg Ala Asn Asn Pro Asp Leu Cys Gly Arg Arg Arg
TABLE-US-00043 TABLE 39 DNA Sequence (SEQ ID NO: 134) and Protein Sequence (SEQ ID NO: 135) of Da1.3 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser tcc act tca ggt cgt cgt gca ttt cat ggc agg aat gcc gca gcc aaa Ser Thr Ser Gly Arg Arg Ala Phe His Gly Arg Asn Ala Ala Ala Lys gcg tct gga ctg gtc ggt ctg act gac agg aga cca caa tgc tgt agt Ala Ser Gly Leu Val Gly Leu Thr Asp Arg Arg Pro Gln Cys Cys Ser gat cct cgc tgt aac gta ggt cat cca gaa ctt tgt ggt gga aga cgc Asp Pro Arg Cys Asn Val Gly His Pro Glu Leu Cys Gly Gly Arg Arg tgatgctcca ggaccctctg aaccacaacg t
TABLE-US-00044 TABLE 40 DNA Sequence (SEQ ID NO: 136) and Protein Sequence (SEQ ID NO: 137) of Da1.4 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser tcc act tca ggt cgt gca ttt cat ggc agg aat gcc gca gcc aaa gcg Ser Thr Ser Gly Arg Ala Phe His Gly Arg Asn Ala Ala Ala Lys Ala tct ggc ctg gtc ggt ctg acc gac aag agg caa gta tgc tgt agt gat Ser Gly Leu Val Gly Leu Thr Asp Lys Arg Gln Val Cys Cys Ser Asp cct cgc tgt aac gta ggt cat cca gaa att tgt ggt gga aga cgc Pro Arg Cys Asn Val Gly His Pro Glu Ile Cys Gly Gly Arg Arg tgatgctcca ggaccctctg aaccacgacg t
TABLE-US-00045 TABLE 41 DNA Sequence (SEQ ID NO: 138) and Protein Sequence (SEQ ID NO: 139) of A1.2 atg ttc acc gtg ttt ctg ttg gtt gtc ttg aca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Thr Thr Thr Val Val Ser ttc cct tca gat agt gca tct ggt ggc agg gat gac gag gcc aaa gac Phe Pro Ser Asp Ser Ala Ser Gly Gly Arg Asp Asp Glu Ala Lys Asp gaa agg tct gac atg tac gaa ttg aaa cgg aat gga cgc tgt tgc cat Glu Arg Ser Asp Met Tyr Glu Leu Lys Arg Asn Gly Arg Cys Cys His cct gcc tgt ggt ggc aaa tac gtt aaa tgt gga cgc tgatgctcca Pro Ala Cys Gly Gly Lys Tyr Val Lys Cys Gly Arg ggaccctctc gaaccacg
TABLE-US-00046 TABLE 42 DNA Sequence (SEQ ID NO: 140) and Protein Sequence (SEQ ID NO: 141) of Bu1.1 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc tct aca gat gat gaa tct gat ggc tcg aat gaa gaa ccc agc gcc Phe Ser Thr Asp Asp Glu Ser Asp Gly Ser Asn Glu Glu Pro Ser Ala gac cag act gcc agg tcc tca atg aac agg gcg cct gga tgc tgt aac Asp Gln Thr Ala Arg Ser Ser Met Asn Arg Ala Pro Gly Cys Cys Asn aat cct gcc tgt gtg aag cac aga tgt gga tgacgctgat gctccaggac Asn Pro Ala Cys Val Lys His Arg Cys Gly cctctgaacc acgacgt
TABLE-US-00047 TABLE 43 DNA Sequence (SEQ ID NO: 142) and Protein Sequence (SEQ ID NO: 143) of Bu1.2 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc tct aca gat gat gaa tct gat ggc tcg aat gaa gaa ccc agc gcc Phe Ser Thr Asp Asp Glu Ser Asp Gly Ser Asn Glu Glu Pro Ser Ala gac cag gct gcc agg tcc gca atg aac agg ccg cct gga tgc tgt aac Asp Gln Ala Ala Arg Ser Ala Met Asn Arg Pro Pro Gly Cys Cys Asn aat cct gcc tgt gtg aag cac aga tgt ggt gga tgacgctgat gctccaggac Asn Pro Ala Cys Val Lys His Arg Cys Gly Gly cctctgaacc acgacgt
TABLE-US-00048 TABLE 44 DNA Sequence (SEQ ID NO: 144) and Protein Sequence (SEQ ID NO: 145) of Bu1.3 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc cct tca gat cgt gac tct gat ggc gcg gat gcc gaa gcc agt gac Phe Pro Ser Asp Arg Asp Ser Asp Gly Ala Asp Ala Glu Ala Ser Asp gag cct gtt gag ttc gaa agg gac gag aat gga tgc tgt tgg aat cct Glu Pro Val Glu Phe Glu Arg Asp Glu Asn Gly Cys Cys Trp Asn Pro tcc tgt ccg agg ccc aga tgt aca gga cga cgc taatgctcca ggaccctctg Ser Cys Pro Arg Pro Arg Cys Thr Gly Arg Arg aaccacgacg t
TABLE-US-00049 TABLE 45 DNA Sequence (SEQ ID NO: 146) and Protein Sequence (SEQ ID NO: 170) of Bu1.4 atg ttc acc gtg ttt ctg ttg gtt gtc ttg aca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Thr Thr Thr Val Val Ser ttc cct tca gat cgt gca tct gat ggc agg aat gcc gca gcc aac gac Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp aaa gcg tct gac gtg gtc acg ctg gtc ctc aag gga tgc tgt tcc acc Lys Ala Ser Asp Val Val Thr Leu Val Leu Lys Gly Cys Cys Ser Thr cct ccc tgt gct gtg ctg tat tgt ggt aga aga cgc tgatgctcca Pro Pro Cys Ala Val Leu Tyr Cys Gly Arg Arg Arg ggaccctctg aaccacgacg t
TABLE-US-00050 TABLE 46 DNA Sequence (SEQ ID NO: 148) and Protein Sequence (SEQ ID NO: 149) of Di1.1 atg ttc acc gtg ttt ctg ttg gtt gtc ttc gca tcc tct gtc acc tta Met Phe Thr Val Phe Leu Leu Val Val Phe Ala Ser Ser Val Thr Leu gat cgt gca tct tat ggc agg tat gcc tca ccc gtc gac aga gcg tct Asp Arg Ala Ser Tyr Gly Arg Tyr Ala Ser Pro Val Asp Arg Ala Ser gcc ctg atc gct cag gcc atc ctt cga gat tgc tgc tcc aat cct cct Ala Leu Ile Ala Gln Ala Ile Leu Arg Asp Cys Cys Ser Asn Pro Pro tgt gcc cat aat aat cca gac tgt cgt taaagacgct gcttgctcca Cys Ala His Asn Asn Pro AspCys Arg ggaccctctg aaccacgacg t
TABLE-US-00051 TABLE 47 DNA Sequence (SEQ ID NO: 150) and Protein Sequence (SEQ ID NO: 151) of T1 gga tgc tgt tct aat cct ccc tgt atc gcg aag aat cca cac atg tgt Gly Cys Cys Ser Asn Pro Pro Cys Ile Ala Lys Asn Pro His Met Cys ggt gga aga cgc tga Gly Gly Arg Arg
TABLE-US-00052 TABLE 48 DNA Sequence (SEQ ID NO: 152) and Protein Sequence (SEQ ID NO: 153) of Cn1.2 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc cct tca gat cgt gca tct gat ggc agg aat gcc gca gcc aac gac Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp aaa gcg tct gac gtg atc acg ctg gcc ctc aag gga tgc tgt tcc aac Lys Ala Ser Asp Val Ile Thr Leu Ala Leu Lys Gly Cys Cys Ser Asn cct gtc tgt cac ttg gag cat tca aac ctt tgt ggt aga aga cgc Pro Val Cys His Leu Glu His Ser Asn Leu Cys Gly Arg Arg Arg tgatgctcca ggaccctctg aaccacgacg t
TABLE-US-00053 TABLE 49 DNA Sequence (SEQ ID NO: 233) and Protein Sequence (SEQ ID NO: 234) of Im1.1 tct gat gga aag agt gcc gcg gcc aaa gcc aaa ccg tct cac ctg acg Ser Asp Gly Lys Ser Ala Ala Ala Lys Ala Lys Pro Ser His Leu Thr gct cca ttc atc agg gac gaa tgc tgt tcc gat tct cgc tgt ggc aag Ala Pro Phe Ile Arg Asp Glu Cys Cys Ser Asp Ser Arg Cys Gly Lys aac tgt ctt tga Asn Cys Leu
TABLE-US-00054 TABLE 50 DNA Sequence (SEQ ID NO: 235) and Protein Sequence (SEQ ID NO: 236) of Im1.2 ttt gat gga agg aat gcc cca gcc gac gac aaa gcg tct gac ctg atc Phe Asp Gly Arg Asn Ala Pro Ala Asp Asp Lys Ala Ser Asp Leu Ile gct caa atc gtc agg aga gca tgc tgt tcc gat cgt cgc tgt aga tgg Ala Gln Ile Val Arg Arg Ala Cys Cys Ser Asp Arg Arg Cys Arg Trp agg tgt ggt tga Arg Cys Gly
TABLE-US-00055 TABLE 51 DNA Sequence (SEQ ID NO: 237) and Protein Sequence (SEQ ID NO: 238) of Rg1.2 tct gat gga agg aat gcc gca gcc gac gcc aga gcg tct ccc cgg atc Ser Asp Gly Arg Asn Ala Ala Ala Asp Ala Arg Ala Ser Pro Arg Ile gct ctt ttc ctc agg ttc aca tgc tgt agg aga ggt acc tgt tcc cag Ala Leu Phe Leu Arg Phe Thr Cys Cys Arg Arg Gly Thr Cys Ser Gln cac tgt ggt tgaagacact gctgctccag gaccctctga accacgacgt His Cys Gly
TABLE-US-00056 TABLE 52 DNA Sequence (SEQ ID NO: 239) and Protein Sequence (SEQ ID NO: 240) of Rg1.6 tct aat gga agg aat gcc gca gcc gac gcc aaa gcg tct caa cgg atc Ser Asn Gly Arg Asn Ala Ala Ala Asp Ala Lys Ala Ser Gln Arg Ile gct cca ttc ctc agg gac tat tgc tgt agg aga cat gcc tgt acg ttg Ala Pro Phe Leu Arg Asp Tyr Cys Cys Arg Arg His Ala Cys Thr Leu att tgt ggt tgaagacgct gctgctccag gaccctctga accacgacgt Ile Cys Gly
TABLE-US-00057 TABLE 53 DNA Sequence (SEQ ID NO: 241) and Protein Sequence (SEQ ID NO: 242) of Rg1.6A tct aat gga agg aat gcc gca gcc gac gcc aaa gcg tct caa cgg atc Ser Asn Gly Arg Asn Ala Ala Ala Asp Ala Lys Ala Ser Gln Arg Ile gct cca ttc ctc agg gac tat tgc tgt agg aga cct ccc tgt acg ttg Ala Pro Phe Leu Arg Asp Tyr Cys Cys Arg Arg Pro Pro Cys Thr Leu att tgt ggt tgaagacgct gctgctccag gaccctctga accacgacgt Ile Cys Gly
TABLE-US-00058 TABLE 54 DNA Sequence (SEQ ID NO: 243) and Protein Sequence (SEQ ID NO: 244) of Rg1.7 tct aat aaa agg aag aat gcc gca atg ctt gac atg atc gct caa cac Ser Asn Lys Arg Lys Asn Ala Ala Met Leu Asp Met Ile Ala Gln His gcc ata agg ggt tgc tgt tcc gat cct cgc tgt aga tat aga tgt cgt Ala Ile Arg Gly Cys Cys Ser Asp Pro Arg Cys Arg Tyr Arg Cys Arg tgaagacgct gctgctccag gaccctctga accacgacgt
TABLE-US-00059 TABLE 55 DNA Sequence (SEQ ID NO: 245) and Protein Sequence (SEQ ID NO: 246) of Rg1.9 ttt aat gga agg agt gcc gca gcc gac caa aat gcg cct ggc ctg atc Phe Asn Gly Arg Ser Ala Ala Ala Asp Gln Asn Ala Pro Gly Leu Ile gct caa gtc gtc aga gga ggg tgc tgt tcc gat ccc cgc tgc gcc tgg Ala Gln Val Val Arg Gly Gly Cys Cys Ser Asp Pro Arg Cys Ala Trp aga tgt ggt tgaagacgtt gctgctccag gaccctctga accacgacgt Arg Cys Gly
TABLE-US-00060 TABLE 56 DNA Sequence (SEQ ID NO: 247) and Protein Sequence (SEQ ID NO: 248) of Rg1.10 ttt gat gga agg aat gcc gca gcc gac gcc aaa gtg att aac acg gtc Phe Asp Gly Arg Asn Ala Ala Ala Asp Ala Lys Val Ile Asn Thr Val gct cga atc gcc tgg gat ata tgc tgt tcc gaa cct gac tgt aac cat Ala Arg Ile Ala Trp Asp Ile Cys Cys Ser Glu Pro Asp Cys Asn His aaa tgt gtt tgaagacgct tctgctccag gaccctctga accacgacgt Lys Cys Val
TABLE-US-00061 TABLE 57 DNA Sequence (SEQ ID NO: 249) and Protein Sequence (SEQ ID NO: 250) of Rg1.11 tct aat aaa agg aag aat gcc gca atg ctt gac atg atc gct caa cac Ser Asn Lys Arg Lys Asn Ala Ala Met Leu Asp Met Ile Ala Gln His gcc ata agg ggt tgc tgt tcc gat cct cgc tgt aaa cat cag tgt ggt Ala Ile Arg Gly Cys Cys Ser Asp Pro Arg Cys Lys His Gln Cys Gly tgaagacgct gctgctccag gaccctctga accacgacgt
TABLE-US-00062 TABLE 58 DNA Sequence (SEQ ID NO: 251) and Protein Sequence (SEQ ID NO: 252) of Ms1.7 atc aag aat aca gca gcc agc aac aaa gcg tct agc ctg gtg gct ctt Ile Lys Asn Thr Ala Ala Ser Asn Lys Ala Ser Ser Leu Val Ala Leu gtt gtc agg gga tgc tgt tac aat cct gtc tgc aag aaa tat tat tgt Val Val Arg Gly Cys Cys Tyr Asn Pro Val Cys Lys Lys Tyr Tyr Cys tgg aaa ggc tgatgctcca ggaccctctg aaccacgacg t Trp Lys Gly
TABLE-US-00063 TABLE 59 DNA Sequence (SEQ ID NO: 253) and Protein Sequence (SEQ ID NO: 254) of P1.7 tct gaa ggc agg aat gct gaa gcc atc gac aac gcc tta gac cag agg Ser Glu Gly Arg Asn Ala Glu Ala Ile Asp Asn Ala Leu Asp Gln Arg gat cca aag cga cag gag ccg ggg tgc tgt agg cat cct gcc tgt ggg Asp Pro Lys Arg Gln Glu Pro Gly Cys Cys Arg His Pro Ala Cys Gly aag aac aga tgt gga aga cgc tgatgctcca ggaccctctg aaccacgacg t Lys Asn Arg Cys Gly Arg Arg
TABLE-US-00064 TABLE 60 DNA Sequence (SEQ ID NO: 255) and Protein Sequence (SEQ ID NO: 256) of Ms1.2 tct gat ggc agg aat att gca gtc gac gac aga tgg tct ttc tat acg Ser Asp Gly Arg Asn Ile Ala Val Asp Asp Arg Trp Ser Phe Tyr Thr ctc ttc cat gct act tgc tgt gcc gat cct gac tgt aga ttc cgg ccc Leu Phe His Ala Thr Cys Cys Ala Asp Pro Asp Cys Arg Phe Arg Pro ggt tgt tgatctttgt tcttcaaaga cgctgctggc ccaggaccct ctgaaccacg Gly Cys acgt
TABLE-US-00065 TABLE 61 DNA Sequence (SEQ ID NO: 257) and Protein Sequence (SEQ ID NO: 258) of Ms1.3 atc aag aat act gca gcc agc aac aaa gcg cct agc ctg gtg gct att Ile Lys Asn Thr Ala Ala Ser Asn Lys Ala Pro Ser Leu Val Ala Ile gcc gtc agg gga tgc tgt tac aat cct tcc tgt tgg ccg aaa aca tat Ala Val Arg Gly Cys Cys Tyr Asn Pro Ser Cys Trp Pro Lys Thr Tyr tgt agt tggaaaggct gatgctccag gaccctctga accacgacgt Cys Ser
TABLE-US-00066 TABLE 62 DNA Sequence (SEQ ID NO: 259) and Protein Sequence (SEQ ID NO: 260) of Ms1.4 tct gat agc agg aat gtc gca atc gag gac aga gtg tct gac ctg cac Ser Asp Ser Arg Asn Val Ala Ile Glu Asp Arg Val Ser Asp Leu His tct atg ttc ttc gat gtt tct tgc tgt agc aat cct acc tgt aaa gaa Ser Met Phe Phe Asp Val Ser Cys Cys Ser Asn Pro Thr Cys Lys Glu acg tat ggt tgt tgatcgttgg ttttgaagac gctgatgctc caggaccctc Thr Tyr Gly Cys
TABLE-US-00067 TABLE 63 DNA Sequence (SEQ ID NO: 261) and Protein Sequence (SEQ ID NO: 262) of Ms1.5 tct gtt ggc agg aat att gca gtc gac gac aga ggg att ttc tct acg Ser Val Gly Arg Asn Ile Ala Val Asp Asp Arg Gly Ile Phe Ser Thr ctc ttc cat gct cat tgc tgt gcc aat ccc atc tgt aaa aac acg ccc Leu Phe His Ala His Cys Cys Ala Asn Pro Ile Cys Lys Asn Thr Pro ggt tgt tgatctttgt tcttcaaaga cgctgctggc ccaggaccct ctgaaccacg Gly Cys acgt
TABLE-US-00068 TABLE 64 DNA Sequence (SEQ ID NO: 263) and Protein Sequence(SEQ ID NO: 264) of Ms1.8 tcc gat ggc agg aat gtc gca atc gac gac aga gtg tct gac ctg cac Ser Asp Gly Arg Asn Val Ala Ile Asp Asp Arg Val Ser Asp Leu His tct atg ttc ttc gat att gct tgc tgt aac aat cct acc tgt aaa gaa Ser Met Phe Phe Asp Ile Ala Cys Cys Asn Asn Pro Thr Cys Lys Glu acg tat ggt tgt tgatcgttgg ttttgaagac gctgatgctc caggaccctc Thr Tyr Gly Cys tgaaccacga cgt
TABLE-US-00069 TABLE 65 DNA Sequence (SEQ ID NO: 265) and Protein Sequence (SEQ ID NO: 266) of Ms1.9 tct gat ggc agg aat gtc gca atc gag gac aga gtg tct gac ctg ctc Ser Asp Gly Arg Asn Val Ala Ile Glu Asp Arg Val Ser Asp Leu Leu tct atg ctc ttc gat gtt gct tgc tgt agc aat cct gtc tgt aaa gaa Ser Met Leu Phe Asp Val Ala Cys Cys Ser Asn Pro Val Cys Lys Glu acg tat ggt tgt tgatcgttgg ttttgaagac gctgatgctc caggaccctc Thr Tyr Gly Cys tgaaccacga cgt
TABLE-US-00070 TABLE 66 DNA Sequence (SEQ ID NO: 267) and Protein Sequence (SEQ ID NO: 268) of Bt1.7 tat gat ggc agg aat gct gcc gcc gac gac aaa gct ttt gac ctg ctg Tyr Asp Gly Arg Asn Ala Ala Ala Asp Asp Lys Ala Phe Asp Leu Leu gct atg acc ata agg gga gga tgc tgt tcc tat cct ccc tgt atc gcg Ala Met Thr Ile Arg Gly Gly Cys Cys Ser Tyr Pro Pro Cys Ile Ala agt aat cct aaa tgt ggt gga aga cgc tgatgctcca ggaccctctg Ser Asn Pro Lys Cys Gly Gly Arg Arg aaccacaacg t
TABLE-US-00071 TABLE 67 DNA Sequence (SEQ ID NO: 269) and Protein Sequence (SEQ ID NO: 270) of Lv1.5 ttt gat ggc agg aat gct gca ggc aac gcc aaa atg tcc gcc ctg atg Phe Asp Gly Arg Asn Ala Ala Gly Asn Ala Lys Met Ser Ala Leu Met gcc ctg acc atc agg gga tgc tgt tcc cat cct gtc tgt agc gcg atg Ala Leu Thr Ile Arg Gly Cys Cys Ser His Pro Val Cys Ser Ala Met agt cca atc tgt ggc tgaagacgct gatgccccag gaccctctga accacgacgt Ser Pro Ile Cys Gly
TABLE-US-00072 TABLE 68 DNA Sequence (SEQ ID NO: 271) and Protein Sequence (SEQ ID NO: 272) of Ms1.10 atc aag aat gct gca gct gac gac aaa gca tct gac ctg ctc tct cag Ile Lys Asn Ala Ala Ala Asp Asp Lys Ala Ser Asp Leu Leu Ser Gln atc gtc agg aat gct gca tcc aat gac aaa ggg tct gac ctg atg act Ile Val Arg Asn Ala Ala Ser Asn Asp Lys Gly Ser Asp Leu Met Thr ctt gcc ctc agg gga tgc tgt aaa aat cct tac tgt ggt gcg tcg aaa Leu Ala Leu Arg Gly Cys Cys Lys Asn Pro Tyr Cys Gly Ala Ser Lys aca tat tgt ggt aga aga cgc tgatgctcca ggaccctctg aaccacgacg t Thr Tyr Cys Gly Arg Arg Arg
TABLE-US-00073 TABLE 69 DNA Sequence (SEQ ID NO: 273) and Protein Sequence (SEQ ID NO: 274) of Om1.1 tctgatggca ggaatgccgc agcgtctgac ctgatggat ctg acc atc aag gga Leu Thr Ile Lys Gly tgc tgt tct tat cct ccc tgt ttc gcg act aat cca gac tgt ggt cga Cys Cys Ser Tyr Pro Pro Cys Phe Ala Thr Asn Pro Asp Cys Gly Arg cga cgc tgatgctcca ggaccctctg aaccacgacg t Arg Arg
TABLE-US-00074 TABLE 70 DNA Sequence (SEQ ID NO: 275) and Protein Sequence (SEQ ID NO: 276) of R1.6 ttt gat ggc agg aat gcc gca gcc gac tac aaa ggg tct gaa ttg ctc Phe Asp Gly Arg Asn Ala Ala Ala Asp Tyr Lys Gly Ser Glu Leu Leu gct atg acc gtc agg gga gga tgc tgt tcc tat cct ccc tgt atc gca Ala Met Thr Val Arg Gly Gly Cys Cys Ser Tyr Pro Pro Cys Ile Ala aat aat cct ctt tgt gct gga aga cgc tga Asn Asn Pro Leu Cys Ala Gly Arg Arg
TABLE-US-00075 TABLE 71 DNA Sequence (SEQ ID NO: 277) and Protein Sequence (SEQ ID NO: 278) of R1.7 ttt gat ggc agg aat gcc gca gcc gac tac aaa ggg tct gaa ttg ctc Phe Asp Gly Arg Asn Ala Ala Ala Asp Tyr Lys Gly Ser Glu Leu Leu gct atg acc gtc agg gga gga tgc tgt tcc tat cct ccc tgt atc gca Ala Met Thr Val Arg Gly Gly Cys Cys Ser Tyr Pro Pro Cys Ile Ala aat aat cct ttt tgt gct gga aga cgc tga Asn Asn Pro Phe Cys Ala Gly Arg Arg
TABLE-US-00076 TABLE 72 DNA Sequence (SEQ ID NO: 279) and Protein Sequence (SEQ ID NO: 280) of Vr1.1 tct tat gac agg tat gcc tcg ccc gtc gac aga gcg tct gcc ctg atc Ser Tyr Asp Arg Tyr Ala Ser Pro Val Asp Arg Ala Ser Ala Leu Ile gct cag gcc atc ctt cga gat tgc tgt tcc aat cct ccc tgt tcc caa Ala Gln Ala Ile Leu Arg Asp Cys Cys Ser Asn Pro Pro Cys Ser Gln aat aat cca gac tgt atg taaagacgct gcttgctcca ggaccctctg Asn Asn Pro Asp Cys Met aaccacgacg t
TABLE-US-00077 TABLE 73 DNA Sequence (SEQ ID NO: 281) and Protein Sequence (SEQ ID NO: 282) of Vr1.2 tct tat ggc agg tat gcc tca ccc gtc gac aga gcg tct gcc ctg atc Ser Tyr Gly Arg Tyr Ala Ser Pro Val Asp Arg Ala Ser Ala Leu Ile gct cag gcc atc ctt cga gat tgc tgc tcc aat cct cct tgt gcc cat Ala Gln Ala Ile Leu Arg Asp Cys Cys Ser Asn Pro Pro Cys Ala His aat aat cca gac tgt cgt taaagacgct gcttgctcca ggaccctctg Asn Asn Pro Asp Cys Arg aaccacgacg t
TABLE-US-00078 TABLE 74 DNA Sequence (SEQ ID NO: 283) and Protein Sequence (SEQ ID NO: 284) of A1.4 tct gat ggc agg aat gcc gca gcc aac gac aaa gcg tct ggc atg agc Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Gly Met Ser gcg ctg gcc gtc aat gaa tgc tgt acc aac cct gtc tgt cac gcg gaa Ala Leu Ala Val Asn Glu Cys Cys Thr Asn Pro Val Cys His Ala Glu cat caa gaa ctt tgt gct aga aga cgc tga His Gln Glu Leu Cys Ala Arg Arg Arg
TABLE-US-00079 TABLE 75 DNA Sequence (SEQ ID NO: 285) and Protein Sequence (SEQ ID NO: 286) of A1.5 tct gat ggc agg aat gcc gca gcc aac gac aaa gcg tct gac gtg atc Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Asp Val Ile acg ctg gcc ctc aag gga tgc tgt tcc aac cct gtc tgt cac ttg gag Thr Leu Ala Leu Lys Gly Cys Cys Ser Asn Pro Val Cys His Leu Glu cat tca aac ctt tgt ggt aga aga cgc tga His Ser Asn Leu Cys Gly Arg Arg Arg
TABLE-US-00080 TABLE 76 DNA Sequence (SEQ ID NO: 287) and Protein Sequence (SEQ ID NO: 288) of A1.6 tct gat ggc agg aat gcc gca gcc aac gac aaa gcg tct ggc atg agc Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Gly Met Ser gcg ctg gcc gtc aat gaa tgc tgt acc aac cct gtc tgt cac gtg gaa Ala Leu Ala Val Asn Glu Cys Cys Thr Asn Pro Val Cys His Val Glu cat caa gaa ctt tgt gct aga aga cgc tga His Gln Glu Leu Cys Ala Arg Arg Arg
TABLE-US-00081 TABLE 77 DNA Sequence (SEQ ID NO: 289) and Protein Sequence (SEQ ID NO: 290) of Af1.1 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca gat cgt gca ttt cgt ggc agg aat gcc gca gcc aaa gcg Phe Thr Ser Asp Arg Ala Phe Arg Gly Arg Asn Ala Ala Ala Lys Ala tct ggc ctg gtc ggt ctg acc gac aag agg caa gaa tgc tgt tct tat Ser Gly Leu Val Gly Leu Thr Asp Lys Arg Gln Glu Cys Cys Ser Tyr cct gcc tgt aac cta gat cat cca gaa ctt tgt ggt tgaagacgct Pro Ala Cys Asn Leu Asp His Pro Glu Leu Cys Gly gatgctccag gaccctctga accacgacgt
TABLE-US-00082 TABLE 78 DNA Sequence (SEQ ID NO: 291) and Protein Sequence (SEQ ID NO: 292) of Af1.2 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser tcc act tca ggt cgt cgt gca ttt cgt ggc agg aat gcc gca gcc aaa Ser Thr Ser Gly Arg Arg Ala Phe Arg Gly Arg Asn Ala Ala Ala Lys gcg tct gga ctg gtc ggt ctg act gac agg aga cca gaa tgc tgt agt Ala Ser Gly Leu Val Gly Leu Thr Asp Arg Arg Pro Glu Cys Cys Ser gat cct cgc tgt aac tcg act cat cca gaa ctt tgt ggt gga aga cgc Asp Pro Arg Cys Asn Ser Thr His Pro Glu Leu Cys Gly Gly Arg Arg tgatgctcca ggaccctctg aaccacgacg t
TABLE-US-00083 TABLE 79 DNA Sequence (SEQ ID NO: 293) and Protein Sequence (SEQ ID NO: 294) of Ar1.2 tct gat ggc agg aat gcc gca gcc aac gcg ttt gac ctg atc gat ctg Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala Phe Asp Leu Ile Asp Leu acc gcc agg cta aat tgc tgt atg att ccc ccc tgt tgg aag aaa tat Thr Ala Arg Leu Asn Cys Cys Met Ile Pro Pro Cys Trp Lys Lys Tyr gga gac aga tgt agt gaa gta cgc tgatgctcca ggaccctctg aaccacgacg Gly Asp Arg Cys Ser Glu Val Arg t
TABLE-US-00084 TABLE 80 DNA Sequence (SEQ ID NO: 295) and Protein Sequence (SEQ ID NO: 296) of Ar1.3 tct gat ggc agg aat gcc gca cgc aaa gcg ttt ggc tgc tgc gac tta Ser Asp Gly Arg Asn Ala Ala Arg Lys Ala Phe Gly Cys Cys Asp Leu ata ccc tgt ttg gag aga tat ggt aac aga tgt aat gaa gtg cac Ile Pro Cys Leu Glu Arg Tyr Gly Asn Arg Cys Asn Glu Val His tgatgctcca ggaccctctg aaccacgcga cgt
TABLE-US-00085 TABLE 81 DNA Sequence (SEQ ID NO: 297) and Protein Sequence (SEQ ID NO: 298) of Ar1.4 tct gat ggc agc aat gcc gca gcc aac gag ttt gac ctg atc gct ctg Ser Asp Gly Ser Asn Ala Ala Ala Asn Glu Phe Asp Leu Ile Ala Leu acc gcc agg cta ggt tgc tgt aac gtt aca ccc tgt tgg gag aaa tat Thr Ala Arg Leu Gly Cys Cys Asn Val Thr Pro Cys Trp Glu Lys Tyr gga gac aaa tgt aat gaa gta cgc tgatgcttca ggaccctctg aaccacgacg Gly Asp Lys Cys Asn Glu Val Arg T
TABLE-US-00086 TABLE 82 DNA Sequence (SEQ ID NO: 299) and Protein Sequence (SEQ ID NO: 300) of Ar1.5 tct gat ggc agg aat gtc gca gca aaa gcg ttt cac cgg atc ggc cgg Ser Asp Gly Arg Asn Val Ala Ala Lys Ala Phe His Arg Ile Gly Arg acc atc agg gat gaa tgc tgt tcc aat cct gcc tgt agg gtg aat aat Thr Ile Arg Asp Glu Cys Cys Ser Asn Pro Ala Cys Arg Val Asn Asn cca cac gtt tgt aga cga cgc tgatgctcca ggaccctctg aaccacgacg t Pro His Val Cys Arg Arg Arg
TABLE-US-00087 TABLE 83 DNA Sequence (SEQ ID NO: 301) and Protein Sequence (SEQ ID NO: 302) of Ar1.6 tct gat ggc agg aat gcc gca gcc aac gcg ttt gac ctg atg cct ctg Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala Phe Asp Leu Met Pro Leu acc gcc agg cta aat tgc tgt agc att ccc ggc tgt tgg aac gaa tat Thr Ala Arg Leu Asn Cys Cys Ser Ile Pro Gly Cys Trp Asn Glu Tyr aaa gac aga tgt agt aaa gta cgc tgatgctcca ggaccctctg aaccacgacg Lys Asp Arg Cys Ser Lys Val Arg t
TABLE-US-00088 TABLE 84 DNA Sequence (SEQ ID NO: 303) and Protein Sequence (SEQ ID NO: 304) of Ay1.2 tctgatggca ggaatgccgc agccgacgac aaagcgtctg acctggtcgc t ctg gtc Leu Val gtc agg gga gga tgc tgt tcc cac cct gtc tgt tac ttt aat aat cca Val Arg Gly Gly Cys Cys Ser His Pro Val Cys Tyr Phe Asn Asn Pro caa atg tgt cgt gga aga cgc tgatgctcca ggaccctctg aaccacgacg t Gln Met Cys Arg Gly Arg Arg
TABLE-US-00089 TABLE 85 DNA Sequence (SEQ ID NO: 305) and Protein Sequence (SEQ ID NO: 306) of Ay1.3 tctgatggca ggaatgccgc agccgacgac aaagcgtctg acctggtcgc t ctg gcc Leu Ala gtc agg gga gga tgc tgt tcc cac cct gtc tgt aac ttg aat aat cca Val Arg Gly Gly Cys Cys Ser His Pro Val Cys Asn Leu Asn Asn Pro caa atg tgt cgt gga aga cgc tgatgctcca ggaccctctg aaccacgacg t Gln Met Cys Arg Gly Arg Arg
TABLE-US-00090 TABLE 86 DNA Sequence (SEQ ID NO: 307) and Protein Sequence (SEQ ID NO: 308) of Bt1.8 ttt cgt ggc agg aat ccc gca gcc aac gac aaa agg tct gac ctg gcc Phe Arg Gly Arg Asn Pro Ala Ala Asn Asp Lys Arg Ser Asp Leu Ala gct ctg agc gtc agg gga gga tgc tgt tcc cat cct gcc tgt agc gtg Ala Leu Ser Val Arg Gly Gly Cys Cys Ser His Pro Ala Cys Ser Val act cat cca gag ctt tgt ggc tgaagacgct gatgccccag gaccctctga Thr His Pro Glu Leu Cys Gly accacgacgt
TABLE-US-00091 TABLE 87 DNA Sequence (SEQ ID NO: 309) and Protein Sequence (SEQ ID NO: 310) of Bt1.9 tct gat ggc ggg aat gcc gca gcc aaa gcg tct gac ctg atc gct cag Ser Asp Gly Gly Asn Ala Ala Ala Lys Ala Ser Asp Leu Ile Ala Gln acc atc agg gga gga tgc tgt tcc tat cct gcc tgt agc gtg gaa cat Thr Ile Arg Gly Gly Cys Cys Ser Tyr Pro Ala Cys Ser Val Glu His caa gac ctt tgt gat gga aga cgc tgatgctcca ggaccctctg aaccacgacg Gln Asp Leu Cys Asp Gly Arg Arg t
TABLE-US-00092 TABLE 88 DNA Sequence (SEQ ID NO: 311) and Protein Sequence (SEQ ID NO: 312) of Ca1.3 tct tat ggc agg aat gcc gca gcc aaa gcg ttt gaa gtg agt tgc tgt Ser Tyr Gly Arg Asn Ala Ala Ala Lys Ala Phe Glu Val Ser Cys Cys gtc gtt cgc ccc tgt tgg att cgc tat caa gag gaa tgt ctt gaa gca Val Val Arg Pro Cys Trp Ile Arg Tyr Gln Glu Glu Cys Leu Glu Ala gat ccc agg acc ctc tga Asp Pro Arg Thr Leu
TABLE-US-00093 TABLE 89 DNA Sequence (SEQ ID NO: 313) and Protein Sequence (SEQ ID NO: 314) of Ca1.4 tct gat ggc agg aat gcc gca gcc aac gcc ctt gac ctg atc act ctg Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala Leu Asp Leu Ile Thr Leu atc gcc agg caa aat tgc tgt agc att ccc ggc tgt tgg gag aaa tat Ile Ala Arg Gln Asn Cys Cys Ser Ile Pro Gly Cys Trp Glu Lys Tyr gga gac aaa tgt agt gaa gta cgc tga Gly Asp Lys Cys Ser Glu Val Arg
TABLE-US-00094 TABLE 90 DNA Sequence (SEQ ID NO: 315) and Protein Sequence (SEQ ID NO: 316) of C1.2 tct gat ggc agg aat gaa gca gcc aac gac gaa gcg tct gac gtg atc Ser Asp Gly Arg Asn Glu Ala Ala Asn Asp Glu Ala Ser Asp Val Ile gag ctg gcc ctc aag gga tgc tgt tcc aac cct gtc tgt cac ttg gag Glu Leu Ala Leu Lys Gly Cys Cys Ser Asn Pro Val Cys His Leu Glu cat cca aac gct tgt ggt aga aga cgc tgatgctcca ggaccctctg His Pro Asn Ala Cys Gly Arg Arg Arg aaccacgacg t
TABLE-US-00095 TABLE 91 DNA Sequence (SEQ ID NO: 317) and Protein Sequence (SEQ ID NO: 318) of C1.3 tct gat ggc agg aat gcc gca gcc aac gac aaa gcg tct gac ctg gtc Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Asp Leu Val gct ctg gcc gtc agg gga tgc tgt tcc aac cct atc tgt tac ttt aat Ala Leu Ala Val Arg Gly Cys Cys Ser Asn Pro Ile Cys Tyr Phe Asn aat cca cga att tgt cgt gga aga cgc tgatgctcca ggaccctctg Asn Pro Arg Ile Cys Arg Gly Arg Arg aaccacgacg t
TABLE-US-00096 TABLE 92 DNA Sequence (SEQ ID NO:3 19) and Protein Sequence (SEQ ID NO: 320) of Ep1.2 tct cat ggc agg aat gcc gca cgc aaa gcg tct gac ctg atc gct ctg Ser His Gly Arg Asn Ala Ala Arg Lys Ala Ser Asp Leu Ile Ala Leu acc gtc agg gaa tgc tgt tct cag cct ccc tgt cgc tgg aaa cat cca Thr Val Arg Glu Cys Cys Ser Gln Pro Pro Cys Arg Trp Lys His Pro gaa ctt tgt agt tga Glu Leu Cys Ser
TABLE-US-00097 TABLE 93 DNA Sequence (SEQ ID NO: 321) and Protein Sequence (SEQ ID NO: 322) of G1.1 tct gat ggc agg aat gac gca gcc aaa gcg ttt gac ctg ata tct tcg Ser Asp Gly Arg Asn Asp Ala Ala Lys Ala Phe Asp Leu Ile Ser Ser acc gtc aag aaa gga tgc tgt tcc cat cct gcc tgt gcg ggg aat aat Thr Val Lys Lys Gly Cys Cys Ser His Pro Ala Cys Ala Gly Asn Asn caa cat att tgt ggc cga aga cgc tgatgctcca ggaccctctg aaccacgacg Gln His Ile Cys Gly Arg Arg Arg t
TABLE-US-00098 TABLE 94 DNA Sequence (SEQ ID NO: 323) and Protein Sequence (SEQ ID NO: 324) of G1.3 tct gat ggc agg aat gcc gca gcc aac gac caa gcg tct gac ctg atg Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Gln Ala Ser Asp Leu Met gct gcg acc gtc agg gga tgc tgt gcc gtt cct tcc tgt cgc ctc cgt Ala Ala Thr Val Arg Gly Cys Cys Ala Val Pro Ser Cys Arg Leu Arg aat cca gac ctt tgt ggt gga gga cgc tgatgctcca ggaccctctg Asn Pro Asp Leu Cys Gly Gly Gly Arg aaccacgacg t
TABLE-US-00099 TABLE 95 DNA Sequence (SEQ ID NO: 325) and Protein Sequence (SEQ ID NO: 326) of Im1.3 ctt gat gaa agg aat gcc gca gcc gac gac aaa gcg tct gac ctg atc Leu Asp Glu Arg Asn Ala Ala Ala Asp Asp Lys Ala Ser Asp Leu Ile gct caa atc gtc agg aga gga tgc tgt tcc cat cct gcc tgt aac gtg Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Ala Cys Asn Val aat aat cca cac att tgt ggt tga Asn Asn Pro His Ile Cys Gly
TABLE-US-00100 TABLE 96 DNA Sequence (SEQ ID NO: 327) and Protein Sequence (SEQ ID NO: 328) of Lv1.2 tct gat ggc agg aat act gca gcc aaa gtc aaa tat tct aag acg ccg Ser Asp Gly Arg Asn Thr Ala Ala Lys Val Lys Tyr Ser Lys Thr Pro gag gaa tgc tgt ccc aat cct ccc tgt ttc gcg aca aat tcg gat att Glu Glu Cys Cys Pro Asn Pro Pro Cys Phe Ala Thr Asn Ser Asp Ile tgt ggc gga aga cgc tgatgctcca ggaccctctg aaccacgacg t Cys Gly Gly Arg Arg
TABLE-US-00101 TABLE 97 DNA Sequence (SEQ ID NO: 329) and Protein Sequence (SEQ ID NO: 330) of Lv1.3 tct aat ggc agg aat gcc gca gcc aaa ttc aaa gcg cct gcc ctg atg Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met aag cgg acc gtc agg gat gct tgc tgt tca gac cct cgc tgt tcc ggg Lys Arg Thr Val Arg Asp Ala Cys Cys Ser Asp Pro Arg Cys Ser Gly aaa cat caa gac ctg tgt ggc tgaagacgct gatgctccag gaccctctga Lys His Gln Asp Leu Cys Gly accacgacgt
TABLE-US-00102 TABLE 98 DNA Sequence (SEQ ID NO: 331) and Protein Sequence (SEQ ID NO: 332) of Lv1.4 tct aat ggc agg aat gcc gca gcc aaa ttc aaa gcg cct gcc ctg atg Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met gag ctg acc gtc agg gaa gat tgc tgt tca gac cct cgc tgt tcc gtg Glu Leu Thr Val Arg Glu Asp Cys Cys Ser Asp Pro Arg Cys Ser Val gga cat caa gac ctg tgt ggc tgaagacgct gatgctccag gaccctctga Gly His Gln Asp Leu Cys Gly Accacgacgt
TABLE-US-00103 TABLE 99 DNA Sequence (SEQ ID NO: 333) and Protein Sequence (SEQ ID NO: 334) of Lv1.6 gca ttt gat ggc agg aat gct gca gcc agc gac aaa gcg tcc gag ctg Ala Phe Asp Gly Arg Asn Ala Ala Ala Ser Asp Lys Ala Ser Glu Leu atg gct ctg gcc gtc agg gga tgc tgt tcc cat cct gcc tgt gct ggg Met Ala Leu Ala Val Arg Gly Cys Cys Ser His Pro Ala Cys Ala Gly agt aat gca cat atc tgt ggc aga aga cgc tgatgctcca ggaccctctg Ser Asn Ala His Ile Cys Gly Arg Arg Arg aaccacgacg t
TABLE-US-00104 TABLE 100 DNA Sequence (SEQ ID NO: 335) and Protein Sequence (SEQ ID NO: 336) of Lv1.7 tct aat ggc agg aat gcc gca gcc aaa ttc aaa gcg cct gcc ctg atg Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met aag ctg acc gtc agg gag gat tgc tgt tca gac cct cgc tgt tcc gtg Lys Leu Thr Val Arg Glu Asp Cys Cys Ser Asp Pro Arg Cys Ser Val gga cat caa gac atg tgt ggc tgaagacgct gatgctccag gaccctctga Gly His Gln Asp Met Cys Gly atcacgacgt
TABLE-US-00105 TABLE 101 DNA Sequence (SEQ ID NO: 337) and Protein Sequence (SEQ ID NO: 338) of Lv1.8 ttt gaa tgc agg aat gct gca ggc aac gac aaa gcg act gac ctg atg Phe Glu Cys Arg Asn Ala Ala Gly Asn Asp Lys Ala Thr Asp Leu Met gct ctg act gtc agg gga tgc tgt tcc cat cct gcc tgt gct ggg aat Ala Leu Thr Val Arg Gly Cys Cys Ser His Pro Ala Cys Ala Gly Asn aat cca cat atc tgc ggc tgaagacgct gatgctccag gaccctctga Asn Pro His Ile Cys Gly accacgacgt
TABLE-US-00106 TABLE 102 DNA Sequence (SEQ ID NO: 339) and Protein Sequence (SEQ ID NO: 340) of Lv1.9 ttt gat ggc agg aac gcc gca gcc aac aac aaa gcg act gat ctg atg Phe Asp Gly Arg Asn Ala Ala Ala Asn Asn Lys Ala Thr Asp Leu Met gct ctg act gtc aga gga tgc tgt ggc aat cct tca tgt agc atc cat Ala Leu Thr Val Arg Gly Cys Cys Gly Asn Pro Ser Cys Ser Ile His att cct tac gtt tgt aat tagagacact gatgctccag gaccctctga Ile Pro Tyr Val Cys Asn accacgacgt
TABLE-US-00107 TABLE 103 DNA Sequence (SEQ ID NO: 341) and Protein Sequence (SEQ ID NO: 342) of Lv1.10 tct aat ggc agg aat gcc gca gcc aaa ttc aaa gcg cct gcc ctg atg Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met aag cgg acc gac agc gaa gaa tgc tgt tta gac tct cgc tgt gcc ggg Lys Arg Thr Asp Ser Glu Glu Cys Cys Leu Asp Ser Arg Cys Ala Gly caa cat caa gac ctg tgt ggc gga aga cgc tgatgctcca ggaccctctg Gln His Gln Asp Leu Cys Gly Gly Arg Arg aaccacgacg t
TABLE-US-00108 TABLE 104 DNA Sequence (SEQ ID NO: 343) and Protein Sequence (SEQ ID NO: 344) of Mr1.3 tct gat ggc agg aat gcc gca gcc aag gac aaa gcg tct gac ctg gtc Ser Asp Gly Arg Asn Ala Ala Ala Lys Asp Lys Ala Ser Asp Leu Val gct ctg acc gtc aag gga tgc tgt tct aat cct ccc tgt tac gcg aat Ala Leu Thr Val Lys Gly Cys Cys Ser Asn Pro Pro Cys Tyr Ala Asn aat caa gcc tat tgt aat gga aga cgc tga Asn Gln Ala Tyr Cys Asn Gly Arg Arg
TABLE-US-00109 TABLE 105 DNA Sequence (SEQ ID NO: 345) and Protein Sequence (SEQ ID NO: 346) of Mr1.4 tct gat ggc agg aat gcc gca gcc aag gac aaa gcg tct gac ctg gtc Ser Asp Gly Arg Asn Ala Ala Ala Lys Asp Lys Ala Ser Asp Leu Val gct ctg acc gtc aag gga tgc tgt tct cat cct gcc tgt agc gtg aat Ala Leu Thr Val Lys Gly Cys Cys Ser His Pro Ala Cys Ser Val Asn aat cca gac att tgt ggt tga Asn Pro Asp Ile Cys Gly
TABLE-US-00110 TABLE 106 DNA Sequence (SEQ ID NO: 347) and Protein Sequence (SEQ ID NO: 348) of Ms1.1 tct gat ggc agg aat gct gca gcc aac aac aaa gtg gct ttg acc atg Ser Asp Gly Arg Asn Ala Ala Ala Asn Asn Lys Val Ala Leu Thr Met agg gga aaa tgc tgt atc aat gat gcg tgt cgc tcg aaa cat cca cag Arg Gly Lys Cys Cys Ile Asn Asp Ala Cys Arg Ser Lys His Pro Gln tac tgt tct gga aga cgc tgatactcca ggaccctctg aaccacgacg t Tyr Cys Ser Gly Arg Arg
TABLE-US-00111 TABLE 107 DNA Sequence (SEQ ID NO: 349) and Protein Sequence (SEQ ID NO: 350) of Ms1.6 tct gat ggc agg aat gct gca gcc aac gac aaa gtg tct gac cag atg Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Val Ser Asp Gln Met gct ctg gtt gtc agg gga tgc tgt tac aat att gcc tgt aga att aat Ala Leu Val Val Arg Gly Cys Cys Tyr Asn Ile Ala Cys Arg Ile Asn aat cca cgg tac tgt cgt gga aaa cgc tgatgttcca ggaccctctg Asn Pro Arg Tyr Cys Arg Gly Lys Arg aaccacgacg t
TABLE-US-00112 TABLE 108 DNA Sequence (SEQ ID NO: 351) and Protein Sequence (SEQ ID NO: 352) of O1.1 tctgaaggca ggaatgccgc agccaacgac aaagcgtctg acctgatggc t ctg aac Leu Asn gtc agg gga tgc tgt tcc cat cct gtc tgt cgc ttc aat tat cca aaa Val Arg Gly Cys Cys Ser His Pro Val Cys Arg Phe Asn Tyr Pro Lys tat tgt ggt gga aga cgc tgatggtcca ggaccctctg aaccacgacg t Tyr Cys Gly Gly Arg Arg
TABLE-US-00113 TABLE 109 DNA Sequence (SEQ ID NO: 353) and Protein Sequence (SEQ ID NO: 354) of O1.2 tctgatggcg ggaatgccgc agcaaaagcg tttgatctaa tcact ctg gcc ctc agg Leu Ala Leu Arg gat gaa tgc tgt gcc agt cct ccc tgt cgt ttg aat aat cca tac gta Asp Glu Cys Cys Ala Ser Pro Pro Cys Arg Leu Asn Asn Pro Tyr Val tgt cat tgacgacgct gatgctccag gaccctctga accacgacgt Cys His
TABLE-US-00114 TABLE 110 DNA Sequence (SEQ ID NO: 355) and Protein Sequence (SEQ ID NO: 356) of O1.4 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ccc act tca gat cgt gca tct gat agg agg aat gcc gca gcc aaa gcg Pro Thr Ser Asp Arg Ala Ser Asp Arg Arg Asn Ala Ala Ala Lys Ala ttt gac ctg aga tat tcg acc gcc aag aga gga tgc tgt tcc aat cct Phe Asp Leu Arg Tyr Ser Thr Ala Lys Arg Gly Cys Cys Ser Asn Pro gtc tgt tgg cag aat aat gca gaa tac tgt cgt gaa agt ggc Val Cys Trp Gln Asn Asn Ala Glu Tyr Cys Arg Glu Ser Gly taatgctcca ggaccctctg aaccacgacg t
TABLE-US-00115 TABLE 111 DNA Sequence (SEQ ID NO: 357) and Protein Sequence (SEQ ID NO: 358) of O1.7 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser ttc act tca gat cgt gca tct gat ggc ggg aat gtc gca gcg tct cac Phe Thr Ser Asp Arg Ala Ser Asp Gly Gly Asn Val Ala Ala Ser His ctg atc gct ctg acc atc aag gga tgc tgt tct cac cct ccc tgt gcc Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser His Pro Pro Cys Ala cag aat aat caa gac tat tgt ggt tgacgacgct gatgctccag gaccctctga Gln Asn Asn Gln Asp Tyr Cys Gly accacgacgt
TABLE-US-00116 TABLE 112 DNA Sequence (SEQ ID NO: 359) and Protein Sequence (SEQ ID NO: 360) of O1.8 atg ttc acc gtg ttt ctg ttg gtt gtc tta tca acc acc gtc gtt tcc Met Phe Thr Val Phe Leu Leu Val Val Leu Ser Thr Thr Val Val Ser tcc act tca gat cgt gca tct gat agg agg aat gcc gca gcc aaa gcg Ser Thr Ser Asp Arg Ala Ser Asp Arg Arg Asn Ala Ala Ala Lys Ala tct gac ctg atg tat tcg acc gtc aag aaa gga tgt tgt tcc cat cct Ser Asp Leu Met Tyr Ser Thr Val Lys Lys Gly Cys Cys Ser His Pro gcc tgt tcg ggg aat aat cga gaa tat tgt cgt gaa agt ggc Ala Cys Ser Gly Asn Asn Arg Glu Tyr Cys Arg Glu Ser Gly taatgctcca ggaccctctg aaccacgacg t
TABLE-US-00117 TABLE 113 DNA Sequence (SEQ ID NO: 361) and Protein Sequence (SEQ ID NO: 362) of Om1.2 tttgatggca ggaatgcctc agccgacagc aaagtggctg cccggatcgc t cag atc Gln Ile gac agg gat cca tgc tgt tcc tat cct gac tgt ggc gcg aat cat cca Asp Arg Asp Pro Cys Cys Ser Tyr Pro Asp Cys Gly Ala Asn His Pro gag att tgt ggt gga aaa cgc tgatgctcca ggaccctctg aaccacgacg t Glu Ile Cys Gly Gly Lys Arg
TABLE-US-00118 TABLE 114 DNA Sequence (SEQ ID NO: 363) and Protein Sequence (SEQ ID NO: 364) of Om1.3 tctcatggca ggaatgccgc acgct ctg acc gtc agg gaa tgc tgt tct cag Leu Thr Val Arg Glu Cys Cys Ser Gln cct cct tgt cgc tgg aaa cat cca gaa ctt tgt agt tgaagacgct Pro Pro Cys Arg Trp Lys His Pro Glu Leu Cys Ser gatgctccag gaccctctga accacgacgt
TABLE-US-00119 TABLE 115 DNA Sequence (SEQ ID NO: 365) and Protein Sequence (SEQ ID NO: 366) of Om1.4 tttgatggca ggaatgctgc agccagcgac aaagcgtctg agctgatggc t ctg gcc Leu Ala gtc agg gga tgc tgt tcc cat cct gcc tgt gct ggg aat aat cca cat Val Arg Gly Cys Cys Ser His Pro Ala Cys Ala Gly Asn Asn Pro His atc tgt ggc aga aga cgc tgatgctcca ggaccctctg aaccacgacg t Ile Cys Gly Arg Arg Arg
TABLE-US-00120 TABLE 116 DNA Sequence (SEQ ID NO: 367) and Protein Sequence (SEQ ID NO: 368) of Om1.5 tctggtgtca ggaaagacgc agcgcctggc ctgatcgct ctg acc atc aag gga Leu Thr Ile Lys Gly tgc tgt tct gat cct agc tgt aac gtg aat aat cca gac tat tgt ggt Cys Cys Ser Asp Pro Ser Cys Asn Val Asn Asn Pro Asp Tyr Cys Gly tgacgacgct gatgctccag gaccctctga accacgacgt
TABLE-US-00121 TABLE 117 DNA Sequence (SEQ ID NO: 369) and Protein Sequence (SEQ ID NO: 370) of Om1.6 tctaatggca ggaatgccgc agccaaattc aaagcgcctg ccctgatgga g ctg acc Leu Thr gtc agg gaa gaa tgc tgt tca gac cct cgc tgt tcc gtg gga cat caa Val Arg Glu Glu Cys Cys Ser Asp Pro Arg Cys Ser Val Gly His Gln gat atg tgt cgg tgaagcacgt gatgctccag gaccctctga accacgacgt Asp Met Cys Arg
TABLE-US-00122 TABLE 118 DNA Sequence (SEQ ID NO: 371) and Protein Sequence (SEQ ID NO: 372) of P1.4 act gat ggc agg aat gct gca gcc ata gcg ctt gac ctg atc gct ccg Thr Asp Gly Arg Asn Ala Ala Ala Ile Ala Leu Asp Leu Ile Ala Pro gcc gtc agg gga gga tgc tgt tcc aat cct gcc tgt tta gtg aat cat Ala Val Arg Gly Gly Cys Cys Ser Asn Pro Ala Cys Leu Val Asn His cta gaa atg tgt ggt aaa aga cgc tgatgcccca ggaccctctg aaccacgacg Leu Glu Met Cys Gly Lys Arg Arg t
TABLE-US-00123 TABLE 119 DNA Sequence (SEQ ID NO: 373) and Protein Sequence (SEQ ID NO: 374) of P1.5 tct gat ggc agg gat gcc gca gcc aac gac aaa gcg tct gac ctg atc Ser Asp Gly Arg Asp Ala Ala Ala Asn Asp Lys Ala Ser Asp Leu Ile gct ctg acc gcc agg aga gat cca tgc tgt ttc aat cct gcc tgt aac Ala Leu Thr Ala Arg Arg Asp Pro Cys Cys Phe Asn Pro Ala Cys Asn gtg aat aat cca cag att tgt ggt tgaagacgct gatgctccag gaccctctga Val Asn Asn Pro Gln Ile Cys Gly accacgacgt
TABLE-US-00124 TABLE 120 DNA Sequence (SEQ ID NO: 375) and Protein Sequence (SEQ ID NO: 376) of P1.6 tct gat ggc agg gat gct gag aaa aca ggc ttt gac acg acc att gtg Ser Asp Gly Arg Asp Ala Glu Lys Thr Gly Phe Asp Thr Thr Ile Val ccg gaa gac tgc tgt tcg gat cct tcc tgt tgg agg ctg cat agt tta Pro Glu Asp Cys Cys Ser Asp Pro Ser Cys Trp Arg Leu His Ser Leu gct tgt act gga att gta aac cgc tgatgctcca ggaccctctg aaccacgacg Ala Cys Thr Gly Ile Val Asn Arg t
TABLE-US-00125 TABLE 121 DNA Sequence (SEQ ID NO: 377) and Protein Sequence (SEQ ID NO: 378) of P1.8 act gat ggc agg agt gct gca gcc ata gcg ttt gcc ctg atc gct ccg Thr Asp Gly Arg Ser Ala Ala Ala Ile Ala Phe Ala Leu Ile Ala Pro acc gtc tgc tgt act aat cct gcc tgt ctc gtg aat aat ata cgc ttt Thr Val Cys Cys Thr Asn Pro Ala Cys Leu Val Asn Asn Ile Arg Phe tgt ggt gga aga cgc tgatgcccca ggaccctctg aaccacgacg t Cys Gly Gly Arg Arg
TABLE-US-00126 TABLE 122 DNA Sequence (SEQ ID NO: 379) and Protein Sequence (SEQ ID NO: 380) of Rg1.1 tct gat gga aga aat gcc gca agc gac gcc aaa gcg ttt ccc cgg atc Ser Asp Gly Arg Asn Ala Ala Ser Asp Ala Lys Ala Phe Pro Arg Ile gct cca atc gtc agg gac gaa tgc tgt agc gat cct agg tgt cac ggg Ala Pro Ile Val Arg Asp Glu Cys Cys Ser Asp Pro Arg Cys His Gly aat aat cgg gac cac tgt gct tgaagacgct gctgctccag gaccctctga Asn Asn Arg Asp His Cys Ala accacgacgt
TABLE-US-00127 TABLE 123 DNA Sequence (SEQ ID NO: 381) and Protein Sequence (SEQ ID NO: 382) of Rg1.3 tct gat ggc agg aat acc gcg gcc gac gaa aaa gcg tcc gac ctg atc Ser Asp Gly Arg Asn Thr Ala Ala Asp Glu Lys Ala Ser Asp Leu Ile tct caa act gtc aag aga gat tgc tgt tcc cat cct ctc tgt aga tta Ser Gln Thr Val Lys Arg Asp Cys Cys Ser His Pro Leu Cys Arg Leu ttt gtt cca gga ctt tgt att tgaagacgct gctgctccag gaccctctga Phe Val Pro Gly Leu Cys Ile accacgact
TABLE-US-00128 TABLE 124 DNA Sequence (SEQ ID NO: 383) and Protein Sequence (SEQ ID NO: 384) of Rg1.4 tct gat ggc agg aat gcc gca gcc gac aac aaa gcg tct gac cta atc Ser Asp Gly Arg Asn Ala Ala Ala Asp Asn Lys Ala Ser Asp Leu Ile gct caa atc gtc agg aga gga tgc tgt tcc cat cct gtc tgt aaa gtg Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Val Cys Lys Val agg tat cca gac ctg tgt cgt tgaagacgct gctgctccag gaccctctga Arg Tyr Pro Asp Leu Cys Arg accacgacgt
TABLE-US-00129 TABLE 125 DNA Sequence (SEQ ID NO: 385) and Protein Sequence (SEQ ID NO: 386) of Rg1.5 tct gat ggc agg aat gcc gca gcc gac aac aga gcg tct gac cta atc Ser Asp Gly Arg Asn Ala Ala Ala Asp Asn Arg Ala Ser Asp Leu Ile gct caa atc gtc agg aga gga tgc tgt tcc cat cct gcc tgt aat gtg Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Ala Cys Asn Val aat aat cca cac att tgt ggt tgaagacgct gctgctccag gaccctctga Asn Asn Pro His Ile Cys Gly accacgacgt
TABLE-US-00130 TABLE 126 DNA Sequence (SEQ ID NO: 387) and Protein Sequence (SEQ ID NO: 388) of Rg1.8 tct gat ggc agg aat gcc gca gcc gac aac aaa ccg tct gac cta atc Ser Asp Gly Arg Asn Ala Ala Ala Asp Asn Lys Pro Ser Asp Leu Ile gct caa atc gtc agg aga gga tgc tgt tcg cat cct gtc tgt aaa gtg Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Val Cys Lys Val agg tat tca gac atg tgt ggt tgaagacgct gctgctccag gaccctctga Arg Tyr Ser Asp Met Cys Gly accacgacgt
TABLE-US-00131 TABLE 127 DNA Sequence (SEQ ID NO: 389) and Protein Sequence (SEQ ID NO: 390) of Sm1.4 tct gat ggc agg aat gca gag cga cga caa agc gtc tgt cct ggt cgc Ser Asp Gly Arg Asn Ala Glu Arg Arg Gln Ser Val Cys Pro Gly Arg tct ggc ccc agg gga gga tgt tgt tcc cac cct gcc tgt aag gtg cat Ser Gly Pro Arg Gly Gly Cys Cys Ser His Pro Ala Cys Lys Val His ttt cca cac agt tgt ggt tgacgacgct gatgctccag gaccctctga Phe Pro His Ser Cys Gly accacgacgt
TABLE-US-00132 TABLE 128 DNA Sequence (SEQ ID NO: 391) and Protein Sequence (SEQ ID NO: 392) of Sm1.5 tct gat ggc agg aat gcc gca gcc agc gac aga gcg tct gac gcg gcc Ser Asp Gly Arg Asn Ala Ala Ala Ser Asp Arg Ala Ser Asp Ala Ala cac cag gta tgc tgt tcc aac cct gtc tgt cac gtg gat cat cca gaa His Gln Val Cys Cys Ser Asn Pro Val Cys His Val Asp His Pro Glu ctt tgt cgt aga aga cgc tgatgctcca ggaccctctg aaccacgacg t Leu Cys Arg Arg Arg Arg
TABLE-US-00133 TABLE 129 DNA Sequence (SEQ ID NO: 393) and Protein Sequence (SEQ ID NO: 394) of S1.5 tct gat ggc agg aat gcc gcg gcc aac gac aaa gcg tct gac ctg gtc Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Asp Leu Val gct ccg gcc atc agg gga tgc tgt tcc cac cct gtc tgt aac ttg agt Ala Pro Ala Ile Arg Gly Cys Cys Ser His Pro Val Cys Asn Leu Ser aat cca caa att tgt cgt gga aga cgc tgatgctcca ggaccctctg Asn Pro Gln Ile Cys Arg Gly Arg Arg aaccacgacg t
TABLE-US-00134 TABLE 130 DNA Sequence (SEQ ID NO: 395) and Protein Sequence (SEQ ID NO: 396) of Tx1.5 ttt cat ggc agg aat gcc gca gcc aaa gcg tct ggc ctg gtc ggt ctg Phe His Gly Arg Asn Ala Ala Ala Lys Ala Ser Gly Leu Val Gly Leu acc gac aag agg caa gaa tgc tgt tct cat cct gcc tgt aac gta gat Thr Asp Lys Arg Gln Glu Cys Cys Ser His Pro Ala Cys Asn Val Asp cat cca gaa att tgt cgt tga His Pro Glu Ile Cys Arg
TABLE-US-00135 TABLE 131 DNA Sequence (SEQ ID NO: 397) and Protein Sequence (SEQ ID NO: 398) of T1.1 act gat ggc agg agt gct gca gcc ata gcg ttt gcc ctg atc gct ccg Thr Asp Gly Arg Ser Ala Ala Ala Ile Ala Phe Ala Leu Ile Ala Pro acc gtc tgg gaa gga tgc tgt tct aat cct gcc tgt ctc gtg aat cat Thr Val Trp Glu Gly Cys Cys Ser Asn Pro Ala Cys Leu Val Asn His ata cgc ttt tgt ggt gga aga cgc tgatgcccca ggaccctctg aaccacgacg Ile Arg Phe Cys Gly Gly Arg Arg t
TABLE-US-00136 TABLE 132 DNA Sequence (SEQ ID NO: 399) and Protein Sequence (SEQ ID NO: 400) of Vr1.3 tct aat ggc atg aat gcc gca gcc atc agg aaa gcg tct gcc ctg gtg Ser Asn Gly Met Asn Ala Ala Ala Ile Arg Lys Ala Ser Ala Leu Val gct cag atc gcc cat cga gac tgc tgt gac gat cct gcc tgc acc gtg Ala Gln Ile Ala His Arg Asp Cys Cys Asp Asp Pro Ala Cys Thr Val aat aat cca ggc ctt tgc act tgaagatgct gctgccccag gaccctctga Asn Asn Pro Gly Leu Cys Thr accacgacgt
TABLE-US-00137 TABLE 133 DNA Sequence (SEQ ID NO: 401) and Protein Sequence (SEQ ID NO: 402) of G1.2 tct gat ggc ggg aat gcc gca gca aaa gag tct gac gtg atc gct ctg Ser Asp Gly Gly Asn Ala Ala Ala Lys Glu Ser Asp Val Ile Ala Leu acc gtc tgg aaa tgc tgt acc att cct tcc tgt tat gag aaa aaa aaa Thr Val Trp Lys Cys Cys Thr Ile Pro Ser Cys Tyr Glu Lys Lys Lys att aaa gca tgt gtc ttt tgacgacgct gatgctccag gaccctctga Ile Lys Ala Cys Val Phe accacgacgt
TABLE-US-00138 TABLE 134 DNA Sequence (SEQ ID NO: 403) and Protein Sequence (SEQ ID NO: 404) of Rg1.12 tct gat ggc gca gtc gac gac aaa gcg ttg gat cga atc gct gaa atc Ser Asp Gly Ala Val Asp Asp Lys Ala Leu Asp Arg Ile Ala Glu Ile gtc agg aga gga tgc tgt ggc aat cct gcc tgt agc ggc tcc tcg aaa Val Arg Arg Gly Cys Cys Gly Asn Pro Ala Cys Ser Gly Ser Ser Lys gat gca ccc tct tgt ggt tgaagacgct gctgctccag gaccctctga Asp Ala Pro Ser Cys Gly accacgacgt
[0199] It will be appreciated that the methods and compositions of the instant invention can be incorporated in the form of a variety of embodiments, only a few of which are disclosed herein. It will be apparent to the artisan that other embodiments exist and do not depart from the spirit of the invention. Thus, the described embodiments are illustrative and should not be construed as restrictive.
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Sequence CWU
1
1
404117PRTArtificial SequenceDescription of Artificial
SequenceAlpha-Conotoxin Peptide Generic Formula I 1Xaa Xaa Xaa Xaa
Xaa Cys Cys Xaa Xaa Xaa Xaa Cys Xaa Xaa Xaa Cys 1 5
10 15 Xaa
221PRTArtificial SequenceDescription of
Artificial SequenceAlpha-Conotoxin Peptide Generic Formula II.
2Xaa Xaa Xaa Xaa Cys Cys Xaa Xaa Xaa Xaa Cys Xaa Xaa Xaa Xaa Xaa 1
5 10 15 Xaa Cys Xaa Xaa Xaa
20
328PRTArtificial SequenceDescription of Artificial
SequenceAlpha-Conotoxin Peptide Generic Formula III. 3Xaa Xaa Xaa
Xaa Xaa Cys Cys Xaa Xaa Xaa Xaa Cys Xaa Xaa Xaa Xaa 1 5
10 15 Xaa Xaa Xaa Cys Xaa Xaa Xaa Xaa
Xaa Xaa Xaa Xaa 20 25
414PRTConus imperialisSITE(2)..(11)Xaa at residue 2 is Glu or
gamma-carboxy-Glu; Xaa at residue 11 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys. 4Asp Xaa Cys Cys Ser Asp Ser Arg
Cys Gly Xaa Asn Cys Leu 1 5 10
512PRTConus imperialisSITE(10)Xaa at residue 10 is Trp (D or
L) or halo-Trp. 5Ala Cys Cys Ser Asp Arg Arg Cys Arg Xaa Arg Cys
1 5 10 613PRTConus
regius 6Phe Thr Cys Cys Arg Arg Gly Thr Cys Ser Gln His Cys
1 5 10 713PRTConus
regiusSITE(2)Xaa at residue 2 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr. 7Asp Xaa Cys
Cys Arg Arg His Ala Cys Thr Leu Ile Cys 1 5
10 813PRTConus regiusSITE(2)..(8)Xaa at residue
2 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr,
O-phospho-Tyr or nitro-Tyr; Xaa at residues 7 and 8 is Pro or
hydroxy-Pro. 8Asp Xaa Cys Cys Arg Arg Xaa Xaa Cys Thr Leu Ile Cys
1 5 10 913PRTConus
regiusSITE(6)..(10)Xaa at residue 6 is Pro or hydroxy-Pro; Xaa at
residue 10 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr,
O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr. 9Gly Cys Cys Ser Asp Xaa
Arg Cys Arg Xaa Arg Cys Arg 1 5
10 1013PRTConus regiusSITE(7)..(11)Xaa at residue 7 is Pro
or hydroxy-Pro; Xaa at residue 11 is Trp (D or L) or halo-Trp.
10Gly Gly Cys Cys Ser Asp Xaa Arg Cys Ala Xaa Arg Cys 1
5 10 1117PRTConus
regiusSITE(3)..(10)Xaa at residue 3 is Trp (D or L) or halo-Trp; Xaa
at residue 9 is Glu or gamma-carboxy-Glu; Xaa at residue 10 is
Pro or hydroxy-Pro. 11Ile Ala Xaa Asp Ile Cys Cys Ser Xaa Xaa Asp Cys Asn
His Xaa Cys 1 5 10 15
Val
1212PRTConus regiusSITE(6)..(9)Xaa at residue 6 is Pro or hydroxy-Pro;
Xaa at residue 9 is Lys, N-methyl-Lys, N,N-dimethyl-Lys or
N,N,N-trimethyl-Lys. 12Gly Cys Cys Ser Asp Xaa Arg Cys Xaa His Gln Cys
1 5 10 1314PRTConus
sponsalisSITE(5)..(11)Xaa at residues 5 and 11 is Pro or hydroxy-Pro;
Xaa at residue 8 is Lys, N-methyl-Lys, N.N-dimethyl-Lys or
N.N.N-trimethyl-Lys. 13Cys Cys Ser Asp Xaa Ala Cys Xaa Gln Thr Xaa Gly
Cys Arg 1 5 10
1413PRTConus sponsalisSITE(3)..(5)Xaa at residue 3 is Glu or
gamma-carboxy-Glu; Xaa at residue 5 is Pro or hydroxy-Pro.
14Cys Cys Xaa Asn Xaa Ala Cys Arg His Thr Gln Gly Cys 1
5 10 1513PRTConus
sulcatusSITE(4)..(12)Xaa at residue 4 is Trp or halo-Trp; Xaa at
residue 6 is Pro or hydroxy-Pro; Xaa at residue 12 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr. 15Gly Cys Cys Xaa His Xaa Ala Cys Gly Arg His Xaa Cys
1 5 10 1614PRTConus
achatinusSITE(2)..(11)Xaa at residues 2 and 7 is Pro or hydroxy-Pro;
Xaa at residue 11 is Lys, N-methyl-Lys, N,N-dimethyl-Lys or
N,N,N-trimethyl-Lys. 16Ala Xaa Cys Cys Asn Asn Xaa Ala Cys Val Xaa His
Arg Cys 1 5 10
1715PRTConus bullatusSITE(2)..(12)Xaa at residues 2 and 8 is Pro or
hydroxy-Pro; Xaa at residue 12 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys. 17Ala Xaa Gly Cys Cys Asn Asn
Xaa Ala Cys Val Xaa His Arg Cys 1 5
10 151814PRTConus bullatusSITE(1)..(11)Xaa at residues
1, 2 and 7 is Pro or hydroxy-Pro; Xaa at residue 11 is Lys,
N-methyl-Lys, N,N-dimethyl-Lys or N,N,N-trimethyl-Lys. 18Xaa Xaa Cys
Cys Asn Asn Xaa Ala Cys Val Xaa His Arg Cys 1 5
10 1916PRTConus bullatusSITE(2)..(13)Xaa at
residue 2 is Glu or gamma-carboxy-Glu; Xaa at residue 6 is Trp
or halo-Trp; Xaa at residues 8 11 and 13 is Pro or hydroxy-Pro.
19Asp Xaa Asn Cys Cys Xaa Asn Xaa Ser Cys Xaa Arg Xaa Arg Cys Thr 1
5 10 15 2013PRTConus
bullatusSITE(6)..(12)Xaa at residues 6 and 7 is Pro or hydroxy-Pro;
Xaa at residue 12 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr,
O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr. 20Gly Cys Cys Ser Arg Xaa
Xaa Cys Ala Val Leu Xaa Cys 1 5
10 2113PRTConus circumcisusSITE(6)Xaa at residue 6 is Pro
or hydroxy-Pro. 21Gly Cys Cys Gly Asn Xaa Asp Cys Thr Ser His Ser Cys
1 5 10 2216PRTConus
stercusmuscarumSITE(6)..(11)Xaa at residue 6 is Pro or hydroxy-Pro;
Xaa at residue 11 is Glu or gamma-carboxy-Glu. 22Gly Cys Cys Ser Asn
Xaa Val Cys His Leu Xaa His Ser Asn Met Cys 1 5
10 15 2317PRTConus obscurusSITE(6)..(15)Xaa at
residue 6 is Pro or hydroxy-Pro; Xaa at residue 14 is Glu or
gamma-carboxy-Glu; Xaa at residue 15 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or 23Gly Cys Cys Ser Asn
Xaa Val Cys Arg Gln Asn Asn Ala Xaa Xaa Cys 1 5
10 15 Arg
2418PRTConus textileSITE(1)..(15)Xaa at residues
1, 7 and 14 is Pro or hydroxy-Pro; Xaa at residue 15 is Glu or
gamma-carboxy-Glu. 24Xaa Gln Cys Cys Ser His Xaa Ala Cys Asn Val Asp His
Xaa Xaa Ile 1 5 10 15
Cys Arg
2518PRTConus radiatusSITE(1)..(15)Xaa at residues 1, 7 and 14 is Pro or
hydroxy-Pro; Xaa at residues 2 and 15 is Glu or
gamma-carboxy-Glu. 25Xaa Xaa Cys Cys Ser His Xaa Ala Cys Asn Val Asp His
Xaa Xaa Ile 1 5 10 15
Cys Arg
2618PRTConus radiatusSITE(1)..(15)Xaa at residues 1, 7 and 14 is Pro or
hydroxy-Pro; Xaa at residue 15 is Glu or gamma-carboxy-Glu. 26Xaa
Gln Cys Cys Ser His Xaa Ala Cys Asn Val Asp His Xaa Xaa Ile 1
5 10 15 Cys Asp
2718PRTConus
omariaSITE(1)..(15)Xaa at residues 1, 7 and 14 is Pro or
hydroxy-Pro; Xaa at residue 15 is Glu or gamma-carboxy-Glu. 27Xaa
Arg Cys Cys Ser His Xaa Ala Cys Asn Val Asp His Xaa Xaa Ile 1
5 10 15 Cys Arg
2818PRTConus
omariaSITE(1)..(14)Xaa at residues 1, 7 and 14 is Pro or
hydroxy-Pro. 28Xaa Gln Cys Cys Ser His Xaa Ala Cys Asn Val Asp His Xaa
Gly Ile 1 5 10 15
Cys Arg
2918PRTConus omariaSITE(1)..(15)Xaa at residues 1, 7 and 14 is Pro or
hydroxy-Pro; Xaa at residue 15 is Glu or gamma-carboxy-Glu. 29Xaa
Gln Cys Cys Ser His Xaa Ala Cys Asn Val Asp His Xaa Xaa Thr 1
5 10 15 Cys Arg
3018PRTConus
omariaSITE(1)..(15)Xaa at residues 1, 7 and 14 is Pro or
hydroxy-Pro; Xaa at residue 15 is Glu or gamma-carboxy-Glu. 30Xaa
Gln Cys Cys Ser His Xaa Ala Cys Asn Val Asp His Xaa Xaa Val 1
5 10 15 Cys Arg
3118PRTConus
omariaSITE(1)..(15)Xaa at residues 1, 7 and 14 is Pro or
hydroxy-Pro; Xaa at residue 15 is Glu or gamma-carboxy-Glu. 31Xaa
Gln Cys Cys Ser His Xaa Ala Cys Asn Ile Asp His Xaa Xaa Ile 1
5 10 15 Cys Arg
3221PRTConus
omariaSITE(1)..(15)Xaa at residues 1, 7 and 14 is Pro or
hydroxy-Pro; Xaa at residue 15 is Glu or gamma-carboxy-Glu. 32Xaa
Gln Cys Cys Ser His Xaa Ala Cys Asn Val Asp His Xaa Xaa Ile 1
5 10 15 Cys Arg Arg Arg Arg
20 3317PRTConus
betulinusSITE(7)..(15)Xaa at residues 7 and 14 is Pro or
hydroxy-Pro; Xaa at residue 15 is Glu or gamma-carboxy-Glu. 33Gly
Gly Cys Cys Ser His Xaa Ala Cys Ala Val Asn His Xaa Xaa Leu 1
5 10 15 Cys
3416PRTConus
betulinusSITE(6)..(14)Xaa at residues 6 and 13 is Pro or
hydroxy-Pro; Xaa at residue 14 is Glu or gamma-carboxy-Glu. 34Gly
Cys Cys Ser His Xaa Ala Cys Ser Val Asn His Xaa Xaa Leu Cys 1
5 10 15 3516PRTConus
dalliSITE(6)..(14)Xaa at residues 6 and 13 is Pro or hydroxy-Pro;
Xaa at residue 14 is Glu or gamma-carboxy-Glu. 35Gly Cys Cys Ser His
Xaa Ala Cys Asn Val Asp His Xaa Xaa Ile Cys 1 5
10 15 3619PRTConus obscurusSITE(6)..(18)Xaa at
residues 6 and 15 is Pro or hydroxy-Pro; Xaa at reside 11 is Lys,
N-methyl-Lys, N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa at
residues 14 and 18 is Glu or gamma-carboxy-Glu. 36Gly Cys Cys Ser His Xaa
Ala Cys Ser Gly Xaa Thr Gln Xaa Xaa Cys 1 5
10 15 Arg Xaa Ser
3718PRTConus tulipaSITE(1)..(14)Xaa at residues 1, 6
and 13 is Pro or hydroxy-Pro; Xaa at residue 14 is Glu or
gamma-carboxy-Glu. 37Xaa Cys Cys Ser His Xaa Ala Cys Ser Gly Asn Asn Xaa
Xaa Phe Cys 1 5 10 15
Arg Gln
3818PRTConus tulipaSITE(6)..(14)Xaa at residues 6 and 13 is Pro or
hydroxy-Pro; Xaa at residue 14 is Glu or gamma-carboxy-Glu. 38Gly
Cys Cys Ser His Xaa Ala Cys Ser Gly Asn Asn Xaa Xaa Phe Cys 1
5 10 15 Arg Gln
3916PRTConus
pennaceusSITE(6)..(15)Xaa at residues 6, 7 and 13 is Pro or
hydroxy-Pro; Xaa at residue 15 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr. 39Gly Cys Cys
Ser His Xaa Xaa Cys Ala Met Asn Asn Xaa Asp Xaa Cys 1 5
10 15 4016PRTConus
pennaceusSITE(6)..(15)Xaa at residuew 6, 7 and 13 is Pro or
hydroxy-Pro; Xaa at residue 15 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr. 40Gly Cys Cys
Ser His Xaa Xaa Cys Phe Leu Asn Asn Xaa Asp Xaa Cys 1 5
10 15 4117PRTConus
textileSITE(6)..(13)Xaa at residues 6, 7 and 13 is Pro or
hydroxy-Pro; Xaa at residue 11 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N.N.N-trimethyl-Lys. 41Gly Cys Cys Ser Asn Xaa Xaa
Cys Ile Ala Xaa Asn Xaa His Met Cys 1 5
10 15 Gly
4216PRTConus distansSITE(6)..(13)Xaa at residues 6, 7
and 13 is Pro or hydroxy-Pro. 42Gly Cys Cys Ser Asn Xaa Xaa Cys Ala
His Asn Asn Xaa Asp Cys Arg 1 5 10
15 4317PRTConus tulipaSITE(6)..(13)Xaa at residues 6 and 13
is Pro or hydroxy-Pro. 43Gly Cys Cys Ser Asn Xaa Ala Cys Ala Gly Asn
Asn Xaa His Val Cys 1 5 10
15 Arg
4416PRTConus dalliSITE(6)..(13)Xaa at residues 6 and 13 is Pro or
hydroxy-Pro. 44Gly Cys Cys Ser Arg Xaa Ala Cys Ile Ala Asn Asn Xaa Asp
Leu Cys 1 5 10 15
4520PRTConus circumcisusSITE(6)..(14)Xaa at residues 6 and 13 is Pro or
hydroxy-Pro; Xaa at residues 11 and 14 is Glu or
gamma-carboxy-Glu. 45Gly Cys Cys Ser Asn Xaa Val Cys His Val Xaa His Xaa
Xaa Leu Cys 1 5 10 15
Arg Arg Arg Arg
204618PRTConus sulcatusSITE(7)..(15)Xaa at residues 7, 12 and 14 is
Pro or hydroxy-Pro; Xaa at residue 11 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa at residue 15 is Glu or
46Gly Gly Cys Cys Ser Phe Xaa Ala Cys Arg Xaa Xaa Arg Xaa Xaa Met 1
5 10 15 Cys Gly
4718PRTConus
textileSITE(1)..(15)Xaa at residues 1, 7 and 14 is Pro or
hydroxy-Pro; Xaa at residues 2 and 15 is Glu or
gamma-carboxy-Glu. 47Xaa Xaa Cys Cys Ser Asp Xaa Arg Cys Asn Ser Ser His
Xaa Xaa Leu 1 5 10 15
Cys Arg
4818PRTConus dalliSITE(1)..(15)Xaa at residues 1, 7 and 14 is Pro or
hydroxy-Pro; Xaa at residue 15 is Glu or gamma-carboxy-Glu. 48Xaa
Gln Cys Cys Ser Asp Xaa Arg Cys Asn Val Gly His Xaa Xaa Leu 1
5 10 15 Cys Gly
4918PRTConus
dalliSITE(1)..(15)Xaa at residue 1 is Gln or pyro-Glu; Xaa at
residues 7 and 14 is Pro or hydroxy-Pro; Xaa at residue 15 is Glu or
gamma-carboxy-Glu. 49Xaa Val Cys Cys Ser Asp Xaa Arg Cys Asn Val Gly His
Xaa Xaa Ile 1 5 10 15
Cys Gly
5016PRTConus textileSITE(6)..(13)Xaa at residues 6, 7 and 13 is Pro or
hydroxy-Pro. 50Gly Cys Cys Ser Arg Xaa Xaa Cys Ile Ala Asn Asn Xaa Asp
Leu Cys 1 5 10 15
5118PRTConus omariaSITE(1)..(15)Xaa at residues 1 and 14 is Pro or
hydroxy-Pro; Xaa at residue 15 is Glu or gamma-carboxy-Glu. 51Xaa
Gln Cys Cys Ser His Leu Ala Cys Asn Val Asp His Xaa Xaa Ile 1
5 10 15 Cys Arg
5219PRTConus
sulcatusSITE(5)..(14)Xaa at residue 5 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr; Xaa at residue 13 is Pro or hydroxy-Pro; Xaa at residue
14 is Glu or 52Gly Cys Cys Ser Xaa Phe Asp Cys Arg Met Met Phe Xaa Xaa
Met Cys 1 5 10 15
Gly Xaa Arg
5318PRTConus sulcatusSITE(11)..(12)Xaa at residue 11 is Lys,
N-methyl-Lys, N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa at
residue 12 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr,
O-sulpho-Tyr, O-phospho-Tyr or 53Gly Gly Cys Cys Ser Phe Ala Ala Cys Arg
Xaa Xaa Arg Xaa Xaa Met 1 5 10
15 Cys Gly
5420PRTConus sulcatusSITE(7)..(15)Xaa at residue 7 is Pro or
hydroxy-Pro; Xaa at residue 10 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr; Xaa at
residue 15 is Glu or 54Gly Gly Cys Cys Phe His Xaa Val Cys Xaa Ile Asn
Leu Leu Xaa Met 1 5 10
15 Cys Arg Gln Arg
205519PRTConus betulinusSITE(7)..(15)Xaa at residues 7, 11 and
14 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr,
O-phospho-Tyr; Xaa at residues 8, 9 and 15 is Pro or hydroxy-Pro.
55Ser Ala Thr Cys Cys Asn Xaa Xaa Xaa Cys Xaa Xaa Thr Xaa Xaa Xaa 1
5 10 15 Ser Cys Leu
5617PRTConus
betulinusSITE(5)..(13)Xaa at residues 5 and 12 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr; Xaa at residues 6, 7 and 13 is Pro or hydroxy-Pro. 56Ala
Cys Cys Ala Xaa Xaa Xaa Cys Phe Xaa Ala Xaa Xaa Xaa Arg Cys 1
5 10 15 Leu
5719PRTConus
betulinusSITE(3)..(16)Xaa at residues 3, 12 and 16 is Glu or
gamma-carboxy-Glu; Xaa at residues 6, 7, 11 and 14 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr. 57Asn Ala Xaa Cys Cys Xaa Xaa Xaa Xaa Cys Xaa Xaa Ala Xaa Xaa
Xaa 1 5 10 15 Ile
Cys Leu
58227DNAConus magusCDS(1)..(189) 58atg ttc acc gtg ttt ctg ttg gtt gtc
ttg gca acc act gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Val
Leu Ala Thr Thr Val Val Ser1 5 10
15 ttc cct tca gat cgt gca tct gat ggc agg aat gcc gca gcc
aac gac 96Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala
Asn Asp 20 25 30 aaa
gcg tct gac gtg atc acg ctg gcc ctc aag gga tgc tgt tcc aac 144Lys
Ala Ser Asp Val Ile Thr Leu Ala Leu Lys Gly Cys Cys Ser Asn 35
40 45 cct gtc tgt cac ttg gag
cat tca aac ctt tgt ggt aga aga cgc 189Pro Val Cys His Leu Glu
His Ser Asn Leu Cys Gly Arg Arg Arg 50 55
60 tgatgctcca ggaccctctg aaccacgacg ttcgagca
2275963PRTConus magus 59Met Phe Thr Val Phe Leu Leu Val Val
Leu Ala Thr Thr Val Val Ser 1 5 10
15 Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala
Ala Asn Asp 20 25 30
Lys Ala Ser Asp Val Ile Thr Leu Ala Leu Lys Gly Cys Cys Ser Asn
35 40 45 Pro Val Cys His
Leu Glu His Ser Asn Leu Cys Gly Arg Arg Arg 50
55 60 60208DNAConus
aulicusCDS(1)..(168) 60atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc
acc gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr
Thr Val Val Ser1 5 10 15
ttc act tca gat cgt gca tct gat ggc agg aag gac gca gcg tct ggc
96Phe Thr Ser Asp Arg Ala Ser Asp Gly Arg Lys Asp Ala Ala Ser Gly
20 25 30 ctg atc gct ctg acc
atc aag gga tgc tgt tct tat cct ccc tgt ttc 144Leu Ile Ala Leu Thr
Ile Lys Gly Cys Cys Ser Tyr Pro Pro Cys Phe 35 40
45 gcg act aat tca gac tat tgt ggt tgacgacgct
gatgctccag gaccctctga 198Ala Thr Asn Ser Asp Tyr Cys Gly
50 55
accacgacgt
2086156PRTConus aulicus 61Met Phe Thr Val Phe Leu Leu Val Val Leu Ala
Thr Thr Val Val Ser 1 5 10
15 Phe Thr Ser Asp Arg Ala Ser Asp Gly Arg Lys Asp Ala Ala Ser
Gly 20 25 30 Leu
Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser Tyr Pro Pro Cys Phe 35
40 45 Ala Thr Asn Ser Asp
Tyr Cys Gly 50 55
62205DNAConus aulicusCDS(1)..(174)
62atg ttc acc gtg ttt ctg ttg gtc gtc ttg gca acc acc gtc gtt tcc
48Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser1
5 10 15 ttc act tca gat cgt
gca tct gat ggc agg aag gac gca gcg tct ggc 96Phe Thr Ser Asp Arg
Ala Ser Asp Gly Arg Lys Asp Ala Ala Ser Gly 20
25 30 ctg att gct ctg acc atg aag gga tgc tgt
tct tat cct ccc tgt ttc 144Leu Ile Ala Leu Thr Met Lys Gly Cys Cys
Ser Tyr Pro Pro Cys Phe 35 40 45
gcg act aat cca gac tgt ggt cga cga cgc tgatgctcca ggaccctctg
194Ala Thr Asn Pro Asp Cys Gly Arg Arg Arg
50 55 aaccacgacg t
2056358PRTConus
aulicus 63Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15 Phe Thr
Ser Asp Arg Ala Ser Asp Gly Arg Lys Asp Ala Ala Ser Gly 20
25 30 Leu Ile Ala Leu Thr Met
Lys Gly Cys Cys Ser Tyr Pro Pro Cys Phe 35 40
45 Ala Thr Asn Pro Asp Cys Gly Arg Arg Arg
50 55
64223DNAConus textileCDS(1)..(192) 64atg ttc acc gtg ttt ctg
ttg gtt gtc ttg gca acc acc gtc gtt tcc 48Met Phe Thr Val Phe Leu
Leu Val Val Leu Ala Thr Thr Val Val Ser1 5
10 15 ttc tct tca ggt cgt agt aca ttt cgt ggc agg
aat gcc gca gcc aaa 96Phe Ser Ser Gly Arg Ser Thr Phe Arg Gly Arg
Asn Ala Ala Ala Lys 20 25 30
gcg tct ggc ctg gtc agt ctg act gac agg aga cca gaa tgc tgt agt
144Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Glu Cys Cys Ser
35 40 45 gat cct cgc tgt
aac tcg agt cat cca gaa ctt tgt ggt gga aga cgc 192Asp Pro Arg Cys
Asn Ser Ser His Pro Glu Leu Cys Gly Gly Arg Arg 50 55
60 tgatgctcca ggaccctctg aaccacgacg t
2236564PRTConus textile 65Met Phe Thr Val
Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Phe Ser Ser Gly Arg Ser Thr Phe
Arg Gly Arg Asn Ala Ala Ala Lys 20 25
30 Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro
Glu Cys Cys Ser 35 40 45
Asp Pro Arg Cys Asn Ser Ser His Pro Glu Leu Cys Gly Gly Arg Arg
50 55 60
66244DNAConus textileCDS(1)..(168) 66atg ttc acc gtg ttt ctg ttg gtt gtc
ttg gca acc gcc gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Val
Leu Ala Thr Ala Val Val Ser1 5 10
15 ttc act tca gat cgt gca tct gat gac ggg aaa gcc gct gcg
tct gac 96Phe Thr Ser Asp Arg Ala Ser Asp Asp Gly Lys Ala Ala Ala
Ser Asp 20 25 30 ctg
atc act ctg acc atc aag gga tgc tgt tct cgt cct ccc tgt atc 144Leu
Ile Thr Leu Thr Ile Lys Gly Cys Cys Ser Arg Pro Pro Cys Ile 35
40 45 gcg aat aat cca gac ttg
tgt ggt tgacgacgct gatgctccag aacggtctga 198Ala Asn Asn Pro Asp Leu
Cys Gly 50 55
accacgacgt tcgagcaatg ttcaccgtgt ttctgttggt
tgtctt 2446756PRTConus textile 67Met Phe Thr Val Phe
Leu Leu Val Val Leu Ala Thr Ala Val Val Ser 1 5
10 15 Phe Thr Ser Asp Arg Ala Ser Asp Asp
Gly Lys Ala Ala Ala Ser Asp 20 25
30 Leu Ile Thr Leu Thr Ile Lys Gly Cys Cys Ser Arg Pro
Pro Cys Ile 35 40 45
Ala Asn Asn Pro Asp Leu Cys Gly
50 55 68223DNAConus
textileCDS(1)..(183) 68atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc
acc gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr
Thr Val Val Ser1 5 10 15
ttc act tca ggt cgt agt aca ttt cgt ggc agg aat gcc gca gcc aaa
96Phe Thr Ser Gly Arg Ser Thr Phe Arg Gly Arg Asn Ala Ala Ala Lys
20 25 30 gcg tct ggc ctg gtc
agt ctg act gac agg aga cca caa tgc tgt tct 144Ala Ser Gly Leu Val
Ser Leu Thr Asp Arg Arg Pro Gln Cys Cys Ser 35 40
45 cat cct gcc tgt aac gta gat cat cca gaa
att tgt cgt tgaagacgct 193His Pro Ala Cys Asn Val Asp His Pro Glu
Ile Cys Arg 50 55 60
gatgctccag gaccctctga accacgacgt
2236961PRTConus textile 69Met Phe Thr Val Phe Leu Leu Val Val Leu Ala
Thr Thr Val Val Ser 1 5 10
15 Phe Thr Ser Gly Arg Ser Thr Phe Arg Gly Arg Asn Ala Ala Ala
Lys 20 25 30 Ala
Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Gln Cys Cys Ser 35
40 45 His Pro Ala Cys Asn
Val Asp His Pro Glu Ile Cys Arg 50 55
60 70223DNAConus radiatusCDS(1)..(183)
70atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
48Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser1
5 10 15 ttc act tca ggt cgt
cgt aca ttt cat ggc agg aat gcc gca gcc aaa 96Phe Thr Ser Gly Arg
Arg Thr Phe His Gly Arg Asn Ala Ala Ala Lys 20
25 30 gcg tct ggc ctg gtc agt ctg act gac agg
aga cca gaa tgc tgt tct 144Ala Ser Gly Leu Val Ser Leu Thr Asp Arg
Arg Pro Glu Cys Cys Ser 35 40 45
cat cct gcc tgt aac gta gat cat cca gaa att tgt cgt tgaagacgct
193His Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Arg
50 55 60 gatgctccag
gaccctctga accacgacgt 2237161PRTConus
radiatus 71Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val
Ser 1 5 10 15 Phe
Thr Ser Gly Arg Arg Thr Phe His Gly Arg Asn Ala Ala Ala Lys
20 25 30 Ala Ser Gly Leu Val
Ser Leu Thr Asp Arg Arg Pro Glu Cys Cys Ser 35
40 45 His Pro Ala Cys Asn Val Asp His Pro
Glu Ile Cys Arg 50 55
60 72223DNAConus radiatusCDS(1)..(183) 72atg ttc acc gtg
ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc 48Met Phe Thr Val
Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser1 5
10 15 ttc act tca ggt cgt agt aca ttt cgt
ggc agg aat gcc gca gcc aaa 96Phe Thr Ser Gly Arg Ser Thr Phe Arg
Gly Arg Asn Ala Ala Ala Lys 20 25
30 gcg tct ggc ctg gtc agt ctg act gac agg aga cca caa tgc
tgt tct 144Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Gln Cys
Cys Ser 35 40 45 cat
cct gcc tgt aac gta gat cat cca gaa att tgc gat tgaagacgct 193His
Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Asp 50
55 60 gatgctccag gaccctctga
accacgacgt 2237361PRTConus radiatus
73Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser 1
5 10 15 Phe Thr Ser Gly
Arg Ser Thr Phe Arg Gly Arg Asn Ala Ala Ala Lys 20
25 30 Ala Ser Gly Leu Val Ser Leu Thr
Asp Arg Arg Pro Gln Cys Cys Ser 35 40
45 His Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys
Asp 50 55 60
74218DNAConus striatusCDS(1)..(171) 74atg ttc act gtg ttt ctg ttg
gtt gtc ttg gca atc act gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu
Val Val Leu Ala Ile Thr Val Val Ser1 5 10
15 ttc cct tta gat cgt gaa tct gat ggc gcg aat gcc
gaa gcc cgc acc 96Phe Pro Leu Asp Arg Glu Ser Asp Gly Ala Asn Ala
Glu Ala Arg Thr 20 25 30
cac gat cat gag aag cac gca ctg gac cgg aat gga tgc tgt agg aat
144His Asp His Glu Lys His Ala Leu Asp Arg Asn Gly Cys Cys Arg Asn
35 40 45 cct gcc tgt gag agc
cac aga tgt ggt tgacgacgct gatgctccag 191Pro Ala Cys Glu Ser
His Arg Cys Gly 50 55
gaccctctga accacgacgt tcgagca
2187557PRTConus striatus 75Met Phe Thr Val Phe Leu Leu Val
Val Leu Ala Ile Thr Val Val Ser 1 5 10
15 Phe Pro Leu Asp Arg Glu Ser Asp Gly Ala Asn Ala
Glu Ala Arg Thr 20 25 30
His Asp His Glu Lys His Ala Leu Asp Arg Asn Gly Cys Cys Arg Asn
35 40 45 Pro Ala Cys
Glu Ser His Arg Cys Gly 50
55 76227DNAConus
bandanusCDS(1)..(180) 76atg ttc acc atg ttt ctg ttg gtt gtc ttg gca acc
act gtc gtt tcc 48Met Phe Thr Met Phe Leu Leu Val Val Leu Ala Thr
Thr Val Val Ser1 5 10 15
ttc gct tca gat cgt gca tct gat ggc agg aat gcc gca gcc aag gac
96Phe Ala Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Lys Asp
20 25 30 aaa gcg tct gac ctg
gtc gct ctg acc gtc aag gga tgc tgt tct cat 144Lys Ala Ser Asp Leu
Val Ala Leu Thr Val Lys Gly Cys Cys Ser His 35 40
45 cct gcc tgt agc gtg aat aat cca gac att
tgt ggt tgaagacgct 190Pro Ala Cys Ser Val Asn Asn Pro Asp Ile
Cys Gly 50 55 60
gatgctccag gaccctctga accacgacgt tcgagca
2277760PRTConus bandanus 77Met Phe Thr Met Phe Leu Leu Val Val Leu Ala
Thr Thr Val Val Ser 1 5 10
15 Phe Ala Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Lys
Asp 20 25 30 Lys
Ala Ser Asp Leu Val Ala Leu Thr Val Lys Gly Cys Cys Ser His 35
40 45 Pro Ala Cys Ser Val
Asn Asn Pro Asp Ile Cys Gly 50 55
60 78104DNAConus bandanusCDS(1)..(54)
78aaa gaa tgc tgt act cat cct gcc tgt cac gtg agt cat cca gaa ctc
48Lys Glu Cys Cys Thr His Pro Ala Cys His Val Ser His Pro Glu Leu1
5 10 15 tgt ggt tgaaaagcga
cgtgacgctc caggaccctc tgaaccacga cgttcgagca 104Cys Gly
7918PRTConus bandanus 79Lys Glu
Cys Cys Thr His Pro Ala Cys His Val Ser His Pro Glu Leu 1
5 10 15 Cys Gly
80206DNAConus
bandanusCDS(1)..(171) 80atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca act
gct gtt ctt cca 48Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr
Ala Val Leu Pro1 5 10 15
gtc act tta gat cgt gca tct gat gga agg aat gca gca gcc aac gcc
96Val Thr Leu Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala
20 25 30 aaa acg cct cgc ctg
atc gcg cca ttc atc agg gat tat tgc tgt cat 144Lys Thr Pro Arg Leu
Ile Ala Pro Phe Ile Arg Asp Tyr Cys Cys His 35 40
45 aga ggt ccc tgt atg gta tgg tgt ggt
tgaagccgct gctgctccag 191Arg Gly Pro Cys Met Val Trp Cys Gly
50 55
gaccctctga accac
2068157PRTConus bandanus 81Met Phe Thr Val Phe Leu Leu Val Val Leu Ala
Thr Ala Val Leu Pro 1 5 10
15 Val Thr Leu Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn
Ala 20 25 30 Lys
Thr Pro Arg Leu Ile Ala Pro Phe Ile Arg Asp Tyr Cys Cys His 35
40 45 Arg Gly Pro Cys Met
Val Trp Cys Gly 50 55
82174DNAConus
caracteristicusCDS(1)..(171) 82atg ttc acc gtg ttt ctg ttg gtt gtc ttg
gca acc act gtg gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Val Leu
Ala Thr Thr Val Val Ser1 5 10
15 ttc act tca gat cgt gct tct gat ggc agg aat gcc gca gcc aac
gcg 96Phe Thr Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn
Ala 20 25 30 ttt gac
ctg atc gct ctg atc gcc agg caa aat tgc tgt agc att ccc 144Phe Asp
Leu Ile Ala Leu Ile Ala Arg Gln Asn Cys Cys Ser Ile Pro 35
40 45 agc tgt tgg gag aaa tat aaa
tgt agt taa 174Ser Cys Trp Glu Lys Tyr Lys
Cys Ser 50 55 8357PRTConus
caracteristicus 83Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val
Val Ser 1 5 10 15
Phe Thr Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala
20 25 30 Phe Asp Leu Ile
Ala Leu Ile Ala Arg Gln Asn Cys Cys Ser Ile Pro 35
40 45 Ser Cys Trp Glu Lys Tyr Lys Cys
Ser 50 55
84219DNAConus caracteristicusCDS(1)..(189) 84atg
ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtg gtt tcc 48Met
Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser1
5 10 15 ttc act tca gat cgt gcg
tct gaa ggc agg aat gct gca gcc aag gac 96Phe Thr Ser Asp Arg Ala
Ser Glu Gly Arg Asn Ala Ala Ala Lys Asp 20 25
30 aaa gcg tct gac ctg gtg gct ctg aca gtc agg
gga tgc tgt gcc att 144Lys Ala Ser Asp Leu Val Ala Leu Thr Val Arg
Gly Cys Cys Ala Ile 35 40 45
cgt gaa tgt cgc ttg cag aat gca gcg tat tgt ggt gga ata tac
189Arg Glu Cys Arg Leu Gln Asn Ala Ala Tyr Cys Gly Gly Ile Tyr 50
55 60 tgatgctcca ggaccctctg
aaccacgacg 2198563PRTConus
caracteristicus 85Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val
Val Ser 1 5 10 15
Phe Thr Ser Asp Arg Ala Ser Glu Gly Arg Asn Ala Ala Ala Lys Asp
20 25 30 Lys Ala Ser Asp
Leu Val Ala Leu Thr Val Arg Gly Cys Cys Ala Ile 35
40 45 Arg Glu Cys Arg Leu Gln Asn Ala
Ala Tyr Cys Gly Gly Ile Tyr 50 55
60 86217DNAConus tulipaCDS(1)..(186) 86atg ttc acc
gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48Met Phe Thr
Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser1 5
10 15 ttc cct tca gat att gca act gag
ggc agg aat gcc gca gcc aaa gcg 96Phe Pro Ser Asp Ile Ala Thr Glu
Gly Arg Asn Ala Ala Ala Lys Ala 20 25
30 ttt gac ctg ata tct tcg atc gtc aag aaa gga tgc tgt
tcc cat cct 144Phe Asp Leu Ile Ser Ser Ile Val Lys Lys Gly Cys Cys
Ser His Pro 35 40 45
gcc tgt tcg ggg aat aat cca gaa ttt tgt cgt caa ggt cgc
186Ala Cys Ser Gly Asn Asn Pro Glu Phe Cys Arg Gln Gly Arg 50
55 60 tgatgctcca ggaccctctg aaccacgacg t
2178762PRTConus tulipa 87Met Phe Thr Val
Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Phe Pro Ser Asp Ile Ala Thr Glu
Gly Arg Asn Ala Ala Ala Lys Ala 20 25
30 Phe Asp Leu Ile Ser Ser Ile Val Lys Lys Gly Cys
Cys Ser His Pro 35 40 45
Ala Cys Ser Gly Asn Asn Pro Glu Phe Cys Arg Gln Gly Arg
50 55 60
88217DNAConus tulipaCDS(1)..(186) 88atg ttc acc gtg ttt ctg ttg gtt gtc
ttg gca acc act gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Val
Leu Ala Thr Thr Val Val Ser1 5 10
15 ttc cct tca gat ata gca act gag ggc agg aat gcc gca gcc
aaa gcg 96Phe Pro Ser Asp Ile Ala Thr Glu Gly Arg Asn Ala Ala Ala
Lys Ala 20 25 30 ttt
gac ctg ata tct tcg atc gtc agg aaa gga tgc tgt tcc aat ccc 144Phe
Asp Leu Ile Ser Ser Ile Val Arg Lys Gly Cys Cys Ser Asn Pro 35
40 45 gcc tgt gcg ggg aat aat
cca cat gtt tgt cgt caa ggt cgc 186Ala Cys Ala Gly Asn Asn
Pro His Val Cys Arg Gln Gly Arg 50 55
60 tgatgctcca ggaccctctg aaccacgacg t
2178962PRTConus tulipa 89Met Phe Thr Val Phe Leu Leu Val Val Leu
Ala Thr Thr Val Val Ser 1 5 10
15 Phe Pro Ser Asp Ile Ala Thr Glu Gly Arg Asn Ala Ala Ala
Lys Ala 20 25 30
Phe Asp Leu Ile Ser Ser Ile Val Arg Lys Gly Cys Cys Ser Asn Pro
35 40 45 Ala Cys Ala Gly
Asn Asn Pro His Val Cys Arg Gln Gly Arg 50
55 60 90226DNAConus
sulcatusCDS(1)..(195) 90atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc
acc gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr
Thr Val Val Ser1 5 10 15
ttc aat tca gat cgt gat cca gca tta ggt ggc agg aat gct gca gcc
96Phe Asn Ser Asp Arg Asp Pro Ala Leu Gly Gly Arg Asn Ala Ala Ala
20 25 30 aaa gcg tct gac aag
atc gct tcg acc ctc aag aga aga gga tgc tgt 144Lys Ala Ser Asp Lys
Ile Ala Ser Thr Leu Lys Arg Arg Gly Cys Cys 35 40
45 tcg tat ttt gac tgt aga atg atg ttt cca
gaa atg tgt ggt tgg cga 192Ser Tyr Phe Asp Cys Arg Met Met Phe Pro
Glu Met Cys Gly Trp Arg 50 55 60
ggc tgatgctcca ggaccctctg aaccacgacg t
226Gly 65
9165PRTConus sulcatus 91Met Phe Thr Val Phe Leu Leu Val Val Leu
Ala Thr Thr Val Val Ser 1 5 10
15 Phe Asn Ser Asp Arg Asp Pro Ala Leu Gly Gly Arg Asn Ala
Ala Ala 20 25 30
Lys Ala Ser Asp Lys Ile Ala Ser Thr Leu Lys Arg Arg Gly Cys Cys
35 40 45 Ser Tyr Phe Asp
Cys Arg Met Met Phe Pro Glu Met Cys Gly Trp Arg 50
55 60 Gly
65
92226DNAConus sulcatusCDS(1)..(195) 92atg ttc acc
gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc 48Met Phe Thr
Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser1 5
10 15 ttc aat tca gat cgt gat cca gca
tta ggt ggc agg aat gct gca gcc 96Phe Asn Ser Asp Arg Asp Pro Ala
Leu Gly Gly Arg Asn Ala Ala Ala 20 25
30 ata gcg tct gac aag atc gct tcg acc ctc agg aga gga
gga tgc tgt 144Ile Ala Ser Asp Lys Ile Ala Ser Thr Leu Arg Arg Gly
Gly Cys Cys 35 40 45
tct ttt cct gcc tgt aga aag tat cgt cca gaa atg tgt ggt gga cga
192Ser Phe Pro Ala Cys Arg Lys Tyr Arg Pro Glu Met Cys Gly Gly Arg 50
55 60 cgc tgatgctcca
ggaccctctg aaccacgacg t 226Arg
65 9365PRTConus
sulcatus 93Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val
Ser 1 5 10 15 Phe
Asn Ser Asp Arg Asp Pro Ala Leu Gly Gly Arg Asn Ala Ala Ala
20 25 30 Ile Ala Ser Asp Lys
Ile Ala Ser Thr Leu Arg Arg Gly Gly Cys Cys 35
40 45 Ser Phe Pro Ala Cys Arg Lys Tyr Arg
Pro Glu Met Cys Gly Gly Arg 50 55
60 Arg
65
94211DNAConus sulcatusCDS(1)..(180) 94atg ttc acc gtg ttt ctg ttg gtt
gtc ttg gca acc acc gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val
Val Leu Ala Thr Thr Val Val Ser1 5 10
15 ttc act tca gat cat gaa tct gat cgc ggt gat gcc caa
acc atc caa 96Phe Thr Ser Asp His Glu Ser Asp Arg Gly Asp Ala Gln
Thr Ile Gln 20 25 30
gaa gtg ttt gag atg ttc gct ctg gac agc gat gga tgc tgt tgg cat
144Glu Val Phe Glu Met Phe Ala Leu Asp Ser Asp Gly Cys Cys Trp His
35 40 45 cct gct tgt ggc aga
cac tat tgt ggt cga aga cgc tgatgctcca 190Pro Ala Cys Gly Arg
His Tyr Cys Gly Arg Arg Arg 50 55
60 ggaccctctg aaccacgacg t
2119560PRTConus sulcatus 95Met Phe Thr Val Phe Leu Leu
Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Phe Thr Ser Asp His Glu Ser Asp Arg Gly Asp
Ala Gln Thr Ile Gln 20 25
30 Glu Val Phe Glu Met Phe Ala Leu Asp Ser Asp Gly Cys Cys Trp
His 35 40 45 Pro
Ala Cys Gly Arg His Tyr Cys Gly Arg Arg Arg 50
55 60 96202DNAConus
sulcatusCDS(1)..(195) 96atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc
acc gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr
Thr Val Val Ser1 5 10 15
ttc aat tca gat cgt gat cca gca tta ggt ggc agg aat gct gca gcc
96Phe Asn Ser Asp Arg Asp Pro Ala Leu Gly Gly Arg Asn Ala Ala Ala
20 25 30 ata gcg tct gac aag
atc gct tcg acc ctc agg aga gga gga tgc tgt 144Ile Ala Ser Asp Lys
Ile Ala Ser Thr Leu Arg Arg Gly Gly Cys Cys 35 40
45 tct ttt gct gcc tgt aga aag tat cgt cca
gaa atg tgt ggt gga cga 192Ser Phe Ala Ala Cys Arg Lys Tyr Arg Pro
Glu Met Cys Gly Gly Arg 50 55 60
cgc tgatgct
202Arg 65 9765PRTConus sulcatus 97Met Phe Thr Val Phe
Leu Leu Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Phe Asn Ser Asp Arg Asp Pro Ala Leu
Gly Gly Arg Asn Ala Ala Ala 20 25
30 Ile Ala Ser Asp Lys Ile Ala Ser Thr Leu Arg Arg Gly
Gly Cys Cys 35 40 45
Ser Phe Ala Ala Cys Arg Lys Tyr Arg Pro Glu Met Cys Gly Gly Arg
50 55 60 Arg
65
98220DNAConus
sulcatusCDS(1)..(189) 98atg ttc acc gtg ttt ctg ttg gtt ctc ttg gca acc
acc gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Leu Leu Ala Thr
Thr Val Val Ser1 5 10 15
ttc aat tca gat cgt gca tta ggt ggc agg aat gct gca gcc aaa gcg
96Phe Asn Ser Asp Arg Ala Leu Gly Gly Arg Asn Ala Ala Ala Lys Ala
20 25 30 tct gac aag atc ctt
tcg aac ctc agg aga gga gga tgc tgt ttt cat 144Ser Asp Lys Ile Leu
Ser Asn Leu Arg Arg Gly Gly Cys Cys Phe His 35 40
45 cct gtc tgt tac atc aat ctt cta gaa atg
tgt cgt caa cga ggc 189Pro Val Cys Tyr Ile Asn Leu Leu Glu Met
Cys Arg Gln Arg Gly 50 55 60
tgatcgtcca ggaccctctg aaccacgacg t
2209963PRTConus sulcatus 99Met Phe Thr Val Phe Leu Leu Val Leu Leu Ala
Thr Thr Val Val Ser 1 5 10
15 Phe Asn Ser Asp Arg Ala Leu Gly Gly Arg Asn Ala Ala Ala Lys
Ala 20 25 30 Ser
Asp Lys Ile Leu Ser Asn Leu Arg Arg Gly Gly Cys Cys Phe His 35
40 45 Pro Val Cys Tyr Ile
Asn Leu Leu Glu Met Cys Arg Gln Arg Gly 50 55
60 100208DNAConus consorsCDS(1)..(177)
100atg ttc acc gtg ttt ctg ttg gtt gtc ttg aca acc act gtc gtt tcc
48Met Phe Thr Val Phe Leu Leu Val Val Leu Thr Thr Thr Val Val Ser1
5 10 15 ttc cct tca gat agt
gca tct gat gtc agg gat gac gaa gcc aaa gac 96Phe Pro Ser Asp Ser
Ala Ser Asp Val Arg Asp Asp Glu Ala Lys Asp 20
25 30 gaa agg tct gac atg tac aaa tcg aaa cgg
aat gga cgc tgt tgc cat 144Glu Arg Ser Asp Met Tyr Lys Ser Lys Arg
Asn Gly Arg Cys Cys His 35 40 45
cct gcc tgt ggc aaa cac ttt agt tgt gga cgc tgatgctcca
ggaccctctg 197Pro Ala Cys Gly Lys His Phe Ser Cys Gly Arg
50 55
aaccacgacg t
20810159PRTConus consors 101Met Phe Thr Val Phe Leu Leu Val Val Leu Thr
Thr Thr Val Val Ser 1 5 10
15 Phe Pro Ser Asp Ser Ala Ser Asp Val Arg Asp Asp Glu Ala Lys
Asp 20 25 30 Glu
Arg Ser Asp Met Tyr Lys Ser Lys Arg Asn Gly Arg Cys Cys His 35
40 45 Pro Ala Cys Gly Lys
His Phe Ser Cys Gly Arg 50 55
102219DNAConus
stercusmuscarumCDS(1)..(189) 102atg ttc acc gtg ttt ctg ttg gtt gtc ttg
gca acc act gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Val Leu
Ala Thr Thr Val Val Ser1 5 10
15 tcc cct tca gat cgt gca tct gat ggc agg aat gcc gca gcc aac
gag 96Ser Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn
Glu 20 25 30 aaa gcg
tct gac gtg atc gcg ctg gcc ctc aag gga tgc tgt tcc aac 144Lys Ala
Ser Asp Val Ile Ala Leu Ala Leu Lys Gly Cys Cys Ser Asn 35
40 45 cct gtc tgt cac ctg gag cat
tca aac atg tgt ggt aga aga cgc 189Pro Val Cys His Leu Glu His
Ser Asn Met Cys Gly Arg Arg Arg 50 55
60 tgatgctcca ggaccctctg aaccacgacg
21910363PRTConus stercusmuscarum 103Met Phe Thr Val Phe Leu Leu
Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Ser Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn
Ala Ala Ala Asn Glu 20 25
30 Lys Ala Ser Asp Val Ile Ala Leu Ala Leu Lys Gly Cys Cys Ser
Asn 35 40 45 Pro
Val Cys His Leu Glu His Ser Asn Met Cys Gly Arg Arg Arg 50
55 60 104248DNAConus
betulinusCDS(1)..(180) 104atg ttc tcc gtg ttt ctg ttg gtt gtc ttg gca acc
act gtc gtt tcc 48Met Phe Ser Val Phe Leu Leu Val Val Leu Ala Thr
Thr Val Val Ser1 5 10 15
tcc act tca ggt ggt gca tct ggt ggc agg aag gct gca gcc aaa gcg
96Ser Thr Ser Gly Gly Ala Ser Gly Gly Arg Lys Ala Ala Ala Lys Ala
20 25 30 tct aac cgg atc gct
ctg acc gtc agg agt gca aca tgc tgt aat tat 144Ser Asn Arg Ile Ala
Leu Thr Val Arg Ser Ala Thr Cys Cys Asn Tyr 35 40
45 cct ccc tgt tac gag act tat cca gaa agt
tgt ctg taacgtgaat 190Pro Pro Cys Tyr Glu Thr Tyr Pro Glu Ser
Cys Leu 50 55 60
catccagagc tttgtggctg aagacactga tgctccagga ccctctgaac cacgacgt
24810560PRTConus betulinus 105Met Phe Ser Val Phe Leu Leu Val Val Leu Ala
Thr Thr Val Val Ser 1 5 10
15 Ser Thr Ser Gly Gly Ala Ser Gly Gly Arg Lys Ala Ala Ala Lys
Ala 20 25 30 Ser
Asn Arg Ile Ala Leu Thr Val Arg Ser Ala Thr Cys Cys Asn Tyr 35
40 45 Pro Pro Cys Tyr Glu
Thr Tyr Pro Glu Ser Cys Leu 50 55
60 106223DNAConus betulinusCDS(1)..(183)
106atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtg gtt tcc
48Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser1
5 10 15 ttc act tca ggt cgt
gca ttt cgt ggc agg aat cgc gca gcc gac gac 96Phe Thr Ser Gly Arg
Ala Phe Arg Gly Arg Asn Arg Ala Ala Asp Asp 20
25 30 aaa agg tct gac ctg gcc gct ctg agc gtc
agg gga gga tgc tgt tcc 144Lys Arg Ser Asp Leu Ala Ala Leu Ser Val
Arg Gly Gly Cys Cys Ser 35 40 45
cat cct gcc tgt gcg gtg aat cat cca gag ctt tgt ggc tgaagacgct
193His Pro Ala Cys Ala Val Asn His Pro Glu Leu Cys Gly
50 55 60 gatgccccag
gaccctctga accacgacgt
22310761PRTConus betulinus 107Met Phe Thr Val Phe Leu Leu Val Val Leu Ala
Thr Thr Val Val Ser 1 5 10
15 Phe Thr Ser Gly Arg Ala Phe Arg Gly Arg Asn Arg Ala Ala Asp
Asp 20 25 30 Lys
Arg Ser Asp Leu Ala Ala Leu Ser Val Arg Gly Gly Cys Cys Ser 35
40 45 His Pro Ala Cys Ala
Val Asn His Pro Glu Leu Cys Gly 50 55
60 108248DNAConus betulinusCDS(1)..(180)
108atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
48Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser1
5 10 15 ttc act tca ggt cgt
gca tct ggt ggc agg aat gct gca gcc aaa gcg 96Phe Thr Ser Gly Arg
Ala Ser Gly Gly Arg Asn Ala Ala Ala Lys Ala 20
25 30 tct aac cgg atc gct atg gcc atc agc agt
gga gca tgc tgt gca tat 144Ser Asn Arg Ile Ala Met Ala Ile Ser Ser
Gly Ala Cys Cys Ala Tyr 35 40 45
cct ccc tgt ttc gag gct tat cca gaa aga tgt ctg taacgtgaat
190Pro Pro Cys Phe Glu Ala Tyr Pro Glu Arg Cys Leu 50
55 60 catccagacc tttgtggctg
aagacgctga tgccccagga ccctctgaac cacgacgt 24810960PRTConus betulinus
109Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser 1
5 10 15 Phe Thr Ser Gly
Arg Ala Ser Gly Gly Arg Asn Ala Ala Ala Lys Ala 20
25 30 Ser Asn Arg Ile Ala Met Ala Ile
Ser Ser Gly Ala Cys Cys Ala Tyr 35 40
45 Pro Pro Cys Phe Glu Ala Tyr Pro Glu Arg Cys Leu
50 55 60
110223DNAConus betulinusCDS(1)..(192) 110atg ttc acc gtg ttt ctg ttg
gtt gtc ttg gca acc act gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu
Val Val Leu Ala Thr Thr Val Val Ser1 5 10
15 ttc act tca gat cgt gca ttt cgt ggc agg aat tcc
gca gcc aac gac 96Phe Thr Ser Asp Arg Ala Phe Arg Gly Arg Asn Ser
Ala Ala Asn Asp 20 25 30
aaa agg tct gac ctg gcc gct ctg agc gtc agg aga gga tgc tgc tcc
144Lys Arg Ser Asp Leu Ala Ala Leu Ser Val Arg Arg Gly Cys Cys Ser
35 40 45 cat ccc gcc tgt agc
gtg aat cat cca gag ctt tgt ggt aga aga cgc 192His Pro Ala Cys Ser
Val Asn His Pro Glu Leu Cys Gly Arg Arg Arg 50 55
60 tgatgcccca ggaccctctg aaccacgacg t
22311164PRTConus betulinus 111Met Phe Thr Val
Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Phe Thr Ser Asp Arg Ala Phe Arg
Gly Arg Asn Ser Ala Ala Asn Asp 20 25
30 Lys Arg Ser Asp Leu Ala Ala Leu Ser Val Arg Arg
Gly Cys Cys Ser 35 40 45
His Pro Ala Cys Ser Val Asn His Pro Glu Leu Cys Gly Arg Arg Arg
50 55 60
112248DNAConus betulinusCDS(1)..(180) 112atg ttc acc gtg ttt ctg ttg gtt
gtc ttg gca acc act gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val
Val Leu Ala Thr Thr Val Val Ser1 5 10
15 ttc act tca ggt cgt gca tct ggt ggc agg aat gct gca
gcc aaa gcg 96Phe Thr Ser Gly Arg Ala Ser Gly Gly Arg Asn Ala Ala
Ala Lys Ala 20 25 30
tct aac cgg atc gct ctg atc gtc agg aat gca gaa tgc tgt tat tat
144Ser Asn Arg Ile Ala Leu Ile Val Arg Asn Ala Glu Cys Cys Tyr Tyr
35 40 45 cct ccc tgt tac gag
gct tat cca gaa att tgt ctg taacgtgaat 190Pro Pro Cys Tyr Glu
Ala Tyr Pro Glu Ile Cys Leu 50 55
60 catccagacc tttgtggctg aagaccctga tgctccagga
ccctctgaac cacgacgt 24811360PRTConus betulinus 113Met Phe Thr Val
Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Phe Thr Ser Gly Arg Ala Ser Gly
Gly Arg Asn Ala Ala Ala Lys Ala 20 25
30 Ser Asn Arg Ile Ala Leu Ile Val Arg Asn Ala Glu
Cys Cys Tyr Tyr 35 40 45
Pro Pro Cys Tyr Glu Ala Tyr Pro Glu Ile Cys Leu
50 55 60
114207DNAConus pennaceusCDS(1)..(168) 114atg ttc acc gtg ttt ctg ttg gtt
gtc ttg gca acc acc gtc att tcc 48Met Phe Thr Val Phe Leu Leu Val
Val Leu Ala Thr Thr Val Ile Ser1 5 10
15 ttc act tca gat cgt gca tct gat ggc ggg aat gcc gca
gcg tct gac 96Phe Thr Ser Asp Arg Ala Ser Asp Gly Gly Asn Ala Ala
Ala Ser Asp 20 25 30
ctg atc gct ctg acc atc aag gga tgc tgt tct cat cct ccc tgt gcc
144Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser His Pro Pro Cys Ala
35 40 45 atg aat aat cca gac
tat tgt ggt tgacgacgct gatgctccag gaccctctga 198Met Asn Asn Pro Asp
Tyr Cys Gly 50 55
accacgacg
20711556PRTConus pennaceus 115Met Phe Thr Val
Phe Leu Leu Val Val Leu Ala Thr Thr Val Ile Ser 1 5
10 15 Phe Thr Ser Asp Arg Ala Ser Asp
Gly Gly Asn Ala Ala Ala Ser Asp 20 25
30 Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser His
Pro Pro Cys Ala 35 40 45
Met Asn Asn Pro Asp Tyr Cys Gly
50 55
116207DNAConus pennaceusCDS(1)..(168) 116atg ttc acc gtg ttt ctg ttg gtt
gtc ttg gca acc acc gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val
Val Leu Ala Thr Thr Val Val Ser1 5 10
15 ttc act tca gat cgt gca tct gat ggc ggg aat gcc gca
atg tct gac 96Phe Thr Ser Asp Arg Ala Ser Asp Gly Gly Asn Ala Ala
Met Ser Asp 20 25 30
ctg atc gct ctg acc atc aag gga tgc tgt tct cat cct ccc tgt ttc
144Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser His Pro Pro Cys Phe
35 40 45 ctg aat aat cca gac
tat tgt ggt tgacgacgct gatgctccag gaccctctga 198Leu Asn Asn Pro Asp
Tyr Cys Gly 50 55
accacgacg
20711756PRTConus pennaceus 117Met Phe Thr Val
Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Phe Thr Ser Asp Arg Ala Ser Asp
Gly Gly Asn Ala Ala Met Ser Asp 20 25
30 Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser His
Pro Pro Cys Phe 35 40 45
Leu Asn Asn Pro Asp Tyr Cys Gly
50 55
118210DNAConus stercusmuscarumCDS(1)..(171) 118atg ttc acc gtg ttt ctg
ttg gtt gtc ttg gca acc act gtc gtt tcc 48Met Phe Thr Val Phe Leu
Leu Val Val Leu Ala Thr Thr Val Val Ser1 5
10 15 ttc cct tca gat cgt gaa tct gat ggc gcg aat
gac gaa gcc cgc acc 96Phe Pro Ser Asp Arg Glu Ser Asp Gly Ala Asn
Asp Glu Ala Arg Thr 20 25 30
gac gag cct gag gag cac gga ccg gac agg aat gga tgc tgt agg aat
144Asp Glu Pro Glu Glu His Gly Pro Asp Arg Asn Gly Cys Cys Arg Asn
35 40 45 cct gcc tgt gag
agc cac aga tgt ggt tgacgacgct gatgctccag 191Pro Ala Cys Glu
Ser His Arg Cys Gly 50 55
gaccctctga accacgacg
21011957PRTConus stercusmuscarum 119Met Phe Thr Val Phe
Leu Leu Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Phe Pro Ser Asp Arg Glu Ser Asp Gly
Ala Asn Asp Glu Ala Arg Thr 20 25
30 Asp Glu Pro Glu Glu His Gly Pro Asp Arg Asn Gly Cys
Cys Arg Asn 35 40 45
Pro Ala Cys Glu Ser His Arg Cys Gly
50 55
120210DNAConus circumcisusCDS(1)..(180) 120atg ttc acc gtg ttt ctg ttg
gtt gtc ttg gca acc act gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu
Val Val Leu Ala Thr Thr Val Val Ser1 5 10
15 ttc cct tca gat cgt gca tct gat ggc agg aat gcc
gca gcc agc gac 96Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala
Ala Ala Ser Asp 20 25 30
aga gcg tct gac gcg gcc cac cag gga tgc tgt tcc aac cct gtc tgt
144Arg Ala Ser Asp Ala Ala His Gln Gly Cys Cys Ser Asn Pro Val Cys
35 40 45 cac gtg gaa cat cca
gaa ctt tgt cgt aga aga cgc tgatgctcca 190His Val Glu His Pro
Glu Leu Cys Arg Arg Arg Arg 50 55
60 ggaccctctg aaccacgacg
21012160PRTConus circumcisus 121Met Phe Thr Val Phe Leu
Leu Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg
Asn Ala Ala Ala Ser Asp 20 25
30 Arg Ala Ser Asp Ala Ala His Gln Gly Cys Cys Ser Asn Pro
Val Cys 35 40 45
His Val Glu His Pro Glu Leu Cys Arg Arg Arg Arg 50
55 60 122213DNAConus
circumcisusCDS(1)..(174) 122atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca
acc act gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Val Leu Ala
Thr Thr Val Val Ser1 5 10
15 ttc cct tca aat cgt gaa tct gat ggc gcg aat gcc gaa gtc cgc acc
96Phe Pro Ser Asn Arg Glu Ser Asp Gly Ala Asn Ala Glu Val Arg Thr
20 25 30 gac gag cct gag
gag cac gac gaa ctg ggc ggg aat gga tgc tgt ggg 144Asp Glu Pro Glu
Glu His Asp Glu Leu Gly Gly Asn Gly Cys Cys Gly 35
40 45 aat cct gac tgt acg agc cac agt tgt
gat tgacgacgct gatgctccag 194Asn Pro Asp Cys Thr Ser His Ser Cys
Asp 50 55
gaccctctga accacgacg
21312358PRTConus circumcisus 123Met Phe Thr Val Phe Leu Leu Val Val
Leu Ala Thr Thr Val Val Ser 1 5 10
15 Phe Pro Ser Asn Arg Glu Ser Asp Gly Ala Asn Ala Glu
Val Arg Thr 20 25 30
Asp Glu Pro Glu Glu His Asp Glu Leu Gly Gly Asn Gly Cys Cys Gly
35 40 45 Asn Pro Asp Cys
Thr Ser His Ser Cys Asp 50
55 124207DNAConus
episcopatusCDS(1)..(168) 124atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca
acc acc gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Val Leu Ala
Thr Thr Val Val Ser1 5 10
15 ttc act tca gat cgt gca tct gat agc agg aag gac gca gcg tct ggc
96Phe Thr Ser Asp Arg Ala Ser Asp Ser Arg Lys Asp Ala Ala Ser Gly
20 25 30 ctg atc gct ctg
acc atc aag gga tgc tgt tct gat cct cgc tgt aac 144Leu Ile Ala Leu
Thr Ile Lys Gly Cys Cys Ser Asp Pro Arg Cys Asn 35
40 45 atg aat aat cca gac tat tgt ggt
tgacgacgct gatgctccag gaccctctga 198Met Asn Asn Pro Asp Tyr Cys Gly
50 55
accacgacg
20712556PRTConus episcopatus 125Met Phe Thr Val Phe Leu Leu
Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Phe Thr Ser Asp Arg Ala Ser Asp Ser Arg Lys
Asp Ala Ala Ser Gly 20 25
30 Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser Asp Pro Arg Cys
Asn 35 40 45 Met
Asn Asn Pro Asp Tyr Cys Gly 50
55 126213DNAConus
sponsalisCDS(1)..(174) 126atg tcc acc gtg ttt ctg ttg gtt gtc ctc gca acc
acc gtc gtt tcc 48Met Ser Thr Val Phe Leu Leu Val Val Leu Ala Thr
Thr Val Val Ser1 5 10 15
ttc act gta gat cgt gca tct gat ggc agg gat gtc gca atc gac gac
96Phe Thr Val Asp Arg Ala Ser Asp Gly Arg Asp Val Ala Ile Asp Asp
20 25 30 aga ttg gtg tct ctc
cct cag atc gcc cat gct gac tgt tgt tcc gat 144Arg Leu Val Ser Leu
Pro Gln Ile Ala His Ala Asp Cys Cys Ser Asp 35 40
45 cct gcc tgc aag cag acg ccc ggt tgt cgt
taaagacgct gctgctccag 194Pro Ala Cys Lys Gln Thr Pro Gly Cys Arg
50 55
gaccctctga accacgacg
21312758PRTConus sponsalis 127Met Ser Thr Val Phe Leu Leu Val Val Leu Ala
Thr Thr Val Val Ser 1 5 10
15 Phe Thr Val Asp Arg Ala Ser Asp Gly Arg Asp Val Ala Ile Asp
Asp 20 25 30 Arg
Leu Val Ser Leu Pro Gln Ile Ala His Ala Asp Cys Cys Ser Asp 35
40 45 Pro Ala Cys Lys Gln
Thr Pro Gly Cys Arg 50 55
128221DNAConus sponsalisCDS(1)..(168)
128atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gct tcc
48Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Ala Ser1
5 10 15 ttc att atc gat gat
cca tct gat ggc agg aat att gca gtc gac gac 96Phe Ile Ile Asp Asp
Pro Ser Asp Gly Arg Asn Ile Ala Val Asp Asp 20
25 30 aga ggg ctt ttc tct acg ctc ttc cat gct
gat tgc tgt gaa aat cct 144Arg Gly Leu Phe Ser Thr Leu Phe His Ala
Asp Cys Cys Glu Asn Pro 35 40 45
gcc tgt aga cac acg cag ggt tgt tgatctttgt tcttcaaaga
cactgctggc 198Ala Cys Arg His Thr Gln Gly Cys
50 55
ccaggaccct ctgaaccacg acg
22112956PRTConus sponsalis 129Met Phe Thr Val Phe Leu Leu Val Val Leu Ala
Thr Thr Val Ala Ser 1 5 10
15 Phe Ile Ile Asp Asp Pro Ser Asp Gly Arg Asn Ile Ala Val Asp
Asp 20 25 30 Arg
Gly Leu Phe Ser Thr Leu Phe His Ala Asp Cys Cys Glu Asn Pro 35
40 45 Ala Cys Arg His Thr
Gln Gly Cys 50 55
130220DNAConus dalliCDS(1)..(180)
130atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
48Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser1
5 10 15 ttc act tca gat cgt
gca ttt cgt ggc agg aat gcc gca gcc aaa gag 96Phe Thr Ser Asp Arg
Ala Phe Arg Gly Arg Asn Ala Ala Ala Lys Glu 20
25 30 tct ggc ctg gtc ggt ctg acc gac aag acg
cga gga tgc tgt tct cat 144Ser Gly Leu Val Gly Leu Thr Asp Lys Thr
Arg Gly Cys Cys Ser His 35 40 45
cct gcc tgt aac gta gat cat cca gaa att tgt ggt tgaagacgct
190Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Gly 50
55 60 gatgctccag gaccctctga
accacgacgt 22013160PRTConus dalli
131Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser 1
5 10 15 Phe Thr Ser Asp
Arg Ala Phe Arg Gly Arg Asn Ala Ala Ala Lys Glu 20
25 30 Ser Gly Leu Val Gly Leu Thr Asp
Lys Thr Arg Gly Cys Cys Ser His 35 40
45 Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Gly
50 55 60
132208DNAConus dalliCDS(1)..(177) 132atg ttc acc gtg ttt ctg ttg gtt
gtc ttg gca acc acc gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val
Val Leu Ala Thr Thr Val Val Ser1 5 10
15 ttc act tca gat ggt gca tct gat gac agg aaa gcc gct
gcg tct gac 96Phe Thr Ser Asp Gly Ala Ser Asp Asp Arg Lys Ala Ala
Ala Ser Asp 20 25 30
ctg atc act ctg acc atc aag gga tgc tgt tct cgt cct ccc tgt atc
144Leu Ile Thr Leu Thr Ile Lys Gly Cys Cys Ser Arg Pro Pro Cys Ile
35 40 45 gcg aat aat cca gac
ttg tgt ggt cga cga cgc tgatgctcca ggaccctctg 197Ala Asn Asn Pro Asp
Leu Cys Gly Arg Arg Arg 50 55
aaccacgacg t
20813359PRTConus dalli 133Met Phe Thr Val
Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Phe Thr Ser Asp Gly Ala Ser Asp
Asp Arg Lys Ala Ala Ala Ser Asp 20 25
30 Leu Ile Thr Leu Thr Ile Lys Gly Cys Cys Ser Arg
Pro Pro Cys Ile 35 40 45
Ala Asn Asn Pro Asp Leu Cys Gly Arg Arg Arg
50 55
134223DNAConus dalliCDS(1)..(192) 134atg ttc acc gtg ttt ctg ttg gtt gtc
ttg gca acc act gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Val
Leu Ala Thr Thr Val Val Ser1 5 10
15 tcc act tca ggt cgt cgt gca ttt cat ggc agg aat gcc gca
gcc aaa 96Ser Thr Ser Gly Arg Arg Ala Phe His Gly Arg Asn Ala Ala
Ala Lys 20 25 30 gcg
tct gga ctg gtc ggt ctg act gac agg aga cca caa tgc tgt agt 144Ala
Ser Gly Leu Val Gly Leu Thr Asp Arg Arg Pro Gln Cys Cys Ser 35
40 45 gat cct cgc tgt aac gta
ggt cat cca gaa ctt tgt ggt gga aga cgc 192Asp Pro Arg Cys Asn Val
Gly His Pro Glu Leu Cys Gly Gly Arg Arg 50 55
60 tgatgctcca ggaccctctg aaccacaacg t
22313564PRTConus dalli 135Met Phe Thr Val Phe Leu
Leu Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Ser Thr Ser Gly Arg Arg Ala Phe His Gly
Arg Asn Ala Ala Ala Lys 20 25
30 Ala Ser Gly Leu Val Gly Leu Thr Asp Arg Arg Pro Gln Cys
Cys Ser 35 40 45
Asp Pro Arg Cys Asn Val Gly His Pro Glu Leu Cys Gly Gly Arg Arg 50
55 60 136220DNAConus
dalliCDS(1)..(189) 136atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act
gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr
Val Val Ser1 5 10 15
tcc act tca ggt cgt gca ttt cat ggc agg aat gcc gca gcc aaa gcg
96Ser Thr Ser Gly Arg Ala Phe His Gly Arg Asn Ala Ala Ala Lys Ala
20 25 30 tct ggc ctg gtc ggt
ctg acc gac aag agg caa gta tgc tgt agt gat 144Ser Gly Leu Val Gly
Leu Thr Asp Lys Arg Gln Val Cys Cys Ser Asp 35 40
45 cct cgc tgt aac gta ggt cat cca gaa att
tgt ggt gga aga cgc 189Pro Arg Cys Asn Val Gly His Pro Glu Ile
Cys Gly Gly Arg Arg 50 55 60
tgatgctcca ggaccctctg aaccacgacg t
22013763PRTConus dalli 137Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr
Thr Val Val Ser 1 5 10
15 Ser Thr Ser Gly Arg Ala Phe His Gly Arg Asn Ala Ala Ala Lys Ala
20 25 30 Ser Gly
Leu Val Gly Leu Thr Asp Lys Arg Gln Val Cys Cys Ser Asp 35
40 45 Pro Arg Cys Asn Val Gly
His Pro Glu Ile Cys Gly Gly Arg Arg 50 55
60 138208DNAConus achatinusCDS(1)..(180)
138atg ttc acc gtg ttt ctg ttg gtt gtc ttg aca acc act gtc gtt tcc
48Met Phe Thr Val Phe Leu Leu Val Val Leu Thr Thr Thr Val Val Ser1
5 10 15 ttc cct tca gat agt
gca tct ggt ggc agg gat gac gag gcc aaa gac 96Phe Pro Ser Asp Ser
Ala Ser Gly Gly Arg Asp Asp Glu Ala Lys Asp 20
25 30 gaa agg tct gac atg tac gaa ttg aaa cgg
aat gga cgc tgt tgc cat 144Glu Arg Ser Asp Met Tyr Glu Leu Lys Arg
Asn Gly Arg Cys Cys His 35 40 45
cct gcc tgt ggt ggc aaa tac gtt aaa tgt gga cgc tgatgctcca
190Pro Ala Cys Gly Gly Lys Tyr Val Lys Cys Gly Arg 50
55 60 ggaccctctc gaaccacg
20813960PRTConus achatinus
139Met Phe Thr Val Phe Leu Leu Val Val Leu Thr Thr Thr Val Val Ser 1
5 10 15 Phe Pro Ser Asp
Ser Ala Ser Gly Gly Arg Asp Asp Glu Ala Lys Asp 20
25 30 Glu Arg Ser Asp Met Tyr Glu Leu
Lys Arg Asn Gly Arg Cys Cys His 35 40
45 Pro Ala Cys Gly Gly Lys Tyr Val Lys Cys Gly Arg
50 55 60
140211DNAConus bullatusCDS(1)..(174) 140atg ttc acc gtg ttt ctg ttg
gtt gtc ttg gca acc act gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu
Val Val Leu Ala Thr Thr Val Val Ser1 5 10
15 ttc tct aca gat gat gaa tct gat ggc tcg aat gaa
gaa ccc agc gcc 96Phe Ser Thr Asp Asp Glu Ser Asp Gly Ser Asn Glu
Glu Pro Ser Ala 20 25 30
gac cag act gcc agg tcc tca atg aac agg gcg cct gga tgc tgt aac
144Asp Gln Thr Ala Arg Ser Ser Met Asn Arg Ala Pro Gly Cys Cys Asn
35 40 45 aat cct gcc tgt gtg
aag cac aga tgt gga tgacgctgat gctccaggac 194Asn Pro Ala Cys Val
Lys His Arg Cys Gly 50 55
cctctgaacc acgacgt
21114158PRTConus bullatus 141Met Phe Thr Val Phe
Leu Leu Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Phe Ser Thr Asp Asp Glu Ser Asp Gly
Ser Asn Glu Glu Pro Ser Ala 20 25
30 Asp Gln Thr Ala Arg Ser Ser Met Asn Arg Ala Pro Gly
Cys Cys Asn 35 40 45
Asn Pro Ala Cys Val Lys His Arg Cys Gly
50 55
142214DNAConus bullatusCDS(1)..(177) 142atg ttc acc gtg ttt ctg ttg gtt
gtc ttg gca acc act gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val
Val Leu Ala Thr Thr Val Val Ser1 5 10
15 ttc tct aca gat gat gaa tct gat ggc tcg aat gaa gaa
ccc agc gcc 96Phe Ser Thr Asp Asp Glu Ser Asp Gly Ser Asn Glu Glu
Pro Ser Ala 20 25 30
gac cag gct gcc agg tcc gca atg aac agg ccg cct gga tgc tgt aac
144Asp Gln Ala Ala Arg Ser Ala Met Asn Arg Pro Pro Gly Cys Cys Asn
35 40 45 aat cct gcc tgt gtg
aag cac aga tgt ggt gga tgacgctgat gctccaggac 197Asn Pro Ala Cys Val
Lys His Arg Cys Gly Gly 50 55
cctctgaacc acgacgt
21414359PRTConus bullatus 143Met Phe Thr
Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Phe Ser Thr Asp Asp Glu Ser
Asp Gly Ser Asn Glu Glu Pro Ser Ala 20 25
30 Asp Gln Ala Ala Arg Ser Ala Met Asn Arg Pro
Pro Gly Cys Cys Asn 35 40 45
Asn Pro Ala Cys Val Lys His Arg Cys Gly Gly
50 55
144208DNAConus bullatusCDS(1)..(177) 144atg ttc acc gtg ttt ctg ttg gtt
gtc ttg gca acc act gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val
Val Leu Ala Thr Thr Val Val Ser1 5 10
15 ttc cct tca gat cgt gac tct gat ggc gcg gat gcc gaa
gcc agt gac 96Phe Pro Ser Asp Arg Asp Ser Asp Gly Ala Asp Ala Glu
Ala Ser Asp 20 25 30
gag cct gtt gag ttc gaa agg gac gag aat gga tgc tgt tgg aat cct
144Glu Pro Val Glu Phe Glu Arg Asp Glu Asn Gly Cys Cys Trp Asn Pro
35 40 45 tcc tgt ccg agg ccc
aga tgt aca gga cga cgc taatgctcca ggaccctctg 197Ser Cys Pro Arg Pro
Arg Cys Thr Gly Arg Arg 50 55
aaccacgacg t
20814559PRTConus bullatus 145Met Phe Thr
Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Phe Pro Ser Asp Arg Asp Ser
Asp Gly Ala Asp Ala Glu Ala Ser Asp 20 25
30 Glu Pro Val Glu Phe Glu Arg Asp Glu Asn Gly
Cys Cys Trp Asn Pro 35 40 45
Ser Cys Pro Arg Pro Arg Cys Thr Gly Arg Arg
50 55
146211DNAConus bullatusCDS(1)..(180) 146atg ttc acc gtg ttt ctg ttg gtt
gtc ttg aca acc act gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val
Val Leu Thr Thr Thr Val Val Ser1 5 10
15 ttc cct tca gat cgt gca tct gat ggc agg aat gcc gca
gcc aac gac 96Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala
Ala Asn Asp 20 25 30
aaa gcg tct gac gtg gtc acg ctg gtc ctc aag gga tgc tgt tcc acc
144Lys Ala Ser Asp Val Val Thr Leu Val Leu Lys Gly Cys Cys Ser Thr
35 40 45 cct ccc tgt gct gtg
ctg tat tgt ggt aga aga cgc tgatgctcca 190Pro Pro Cys Ala Val
Leu Tyr Cys Gly Arg Arg Arg 50 55
60 ggaccctctg aaccacgacg t
21114760PRTConus bullatus 147Met Phe Thr Val Phe Leu Leu
Val Val Leu Thr Thr Thr Val Val Ser 1 5
10 15 Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn
Ala Ala Ala Asn Asp 20 25
30 Lys Ala Ser Asp Val Val Thr Leu Val Leu Lys Gly Cys Cys Ser
Thr 35 40 45 Pro
Pro Cys Ala Val Leu Tyr Cys Gly Arg Arg Arg 50
55 60 148212DNAConus
distansCDS(1)..(171) 148atg ttc acc gtg ttt ctg ttg gtt gtc ttc gca tcc
tct gtc acc tta 48Met Phe Thr Val Phe Leu Leu Val Val Phe Ala Ser
Ser Val Thr Leu1 5 10 15
gat cgt gca tct tat ggc agg tat gcc tca ccc gtc gac aga gcg tct
96Asp Arg Ala Ser Tyr Gly Arg Tyr Ala Ser Pro Val Asp Arg Ala Ser
20 25 30 gcc ctg atc gct cag
gcc atc ctt cga gat tgc tgc tcc aat cct cct 144Ala Leu Ile Ala Gln
Ala Ile Leu Arg Asp Cys Cys Ser Asn Pro Pro 35 40
45 tgt gcc cat aat aat cca gac tgt cgt
taaagacgct gcttgctcca 191Cys Ala His Asn Asn Pro Asp Cys Arg
50 55
ggaccctctg aaccacgacg t
21214957PRTConus distans 149Met Phe Thr Val Phe Leu Leu Val Val Phe Ala
Ser Ser Val Thr Leu 1 5 10
15 Asp Arg Ala Ser Tyr Gly Arg Tyr Ala Ser Pro Val Asp Arg Ala
Ser 20 25 30 Ala
Leu Ile Ala Gln Ala Ile Leu Arg Asp Cys Cys Ser Asn Pro Pro 35
40 45 Cys Ala His Asn Asn
Pro Asp Cys Arg 50 55
15063DNAConus textileCDS(1)..(60)
150gga tgc tgt tct aat cct ccc tgt atc gcg aag aat cca cac atg tgt
48Gly Cys Cys Ser Asn Pro Pro Cys Ile Ala Lys Asn Pro His Met Cys1
5 10 15 ggt gga aga cgc tga
63Gly Gly Arg Arg
20 15120PRTConus textile 151Gly Cys Cys Ser Asn Pro Pro Cys
Ile Ala Lys Asn Pro His Met Cys 1 5 10
15 Gly Gly Arg Arg
20
152220DNAConus consorsCDS(1)..(189) 152atg ttc acc gtg ttt ctg ttg
gtt gtc ttg gca acc act gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu
Val Val Leu Ala Thr Thr Val Val Ser1 5 10
15 ttc cct tca gat cgt gca tct gat ggc agg aat gcc
gca gcc aac gac 96Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala
Ala Ala Asn Asp 20 25 30
aaa gcg tct gac gtg atc acg ctg gcc ctc aag gga tgc tgt tcc aac
144Lys Ala Ser Asp Val Ile Thr Leu Ala Leu Lys Gly Cys Cys Ser Asn
35 40 45 cct gtc tgt cac ttg
gag cat tca aac ctt tgt ggt aga aga cgc 189Pro Val Cys His Leu
Glu His Ser Asn Leu Cys Gly Arg Arg Arg 50 55
60 tgatgctcca ggaccctctg aaccacgacg t
22015363PRTConus consors 153Met Phe Thr Val Phe Leu Leu
Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn
Ala Ala Ala Asn Asp 20 25
30 Lys Ala Ser Asp Val Ile Thr Leu Ala Leu Lys Gly Cys Cys Ser
Asn 35 40 45 Pro
Val Cys His Leu Glu His Ser Asn Leu Cys Gly Arg Arg Arg 50
55 60 15415PRTConus
musicusSITE(4)..(12)Xaa at residues 4, 11 and 12 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr. Xaa at residue 6 is Pro or hydroxy-Pro. 154Gly Cys Cys
Xaa Asn Xaa Val Cys Xaa Xaa Xaa Xaa Cys Xaa Xaa 1 5
10 1515516PRTConus
purpurascensSITE(1)..(3)Xaa at residue 1 is Gln or pyro-Glu; Xaa at
residue 2 is Glu or gamma-carboxy-Glu; Xaa at residues 3 and 9 is
Pro or hydroxy-Pro. 155Xaa Xaa Xaa Gly Cys Cys Arg His Xaa Ala Cys Gly
Xaa Asn Arg Cys 1 5 10
15 15613PRTConus musicusSITE(5)..(11)Xaa at residues 5 and 11 is Pro
or hydroxy-Pro. 156Cys Cys Ala Asp Xaa Asp Cys Arg Phe Arg Xaa Gly Cys
1 5 10 15717PRTConus
musicusSITE(4)..(13)Xaa at residues 4 and 13 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr; Xaa at residues 6 and 10 is Pro or hydroxy-Pro. 157Gly
Cys Cys Xaa Asn Xaa Ser Cys Xaa Xaa Xaa Thr Xaa Cys Ser Xaa 1
5 10 15 Xaa
15813PRTConus
musicusSITE(5)..(8)Xaa at residue 5 is Pro or hydroxy-Pro; Xaa at
residue 8 is Lys, N-methyl-Lys, N,N-dimethyl-Lys or
N,N,N-trimethyl-Lys. 158Cys Cys Ser Asn Xaa Thr Cys Xaa Xaa Thr Xaa Gly
Cys 1 5 10
15913PRTConus musicusSITE(5)..(11)Xaa at residues 5 and 11 is Pro or
hydroxy-Pro; Xaa at residue 8 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys. 159Cys Cys Ala Asn Xaa Ile Cys
Xaa Asn Thr Xaa Gly Cys 1 5
10 16013PRTConus musicusSITE(5)..(8)Xaa at residue 5 is Pro or
hydroxy-Pro; Xaa at residue 8 is Lys, N-methyl-Lys, N,N-dimethyl-Lys
or N,N,N-trimethyl-Lys. 160Cys Cys Asn Asn Xaa Thr Cys Xaa Xaa Thr
Xaa Gly Cys 1 5 10
16113PRTConus musicusSITE(5)..(8)Xaa at residue 5 is Pro or hydroxy-Pro;
Xaa at residue 8 is Lys, N-methyl-Lys, N,N-dimethyl-Lys or
N,N,N-trimethyl-Lys. 161Cys Cys Ser Asn Xaa Val Cys Xaa Xaa Thr Xaa Gly
Cys 1 5 10
16217PRTConus betulinusSITE(6)..(14)Xaa at residue 6 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr; Xaa at residues 7, 8 and 14 is Pro or hydroxy-Pro. 162Gly
Gly Cys Cys Ser Xaa Xaa Xaa Cys Ile Ala Ser Asn Xaa Xaa Cys 1
5 10 15 Gly
16315PRTConus
lividusSITE(6)..(13)Xaa at residues 6 and 13 is Pro or hydroxy-Pro.
163Gly Cys Cys Ser His Xaa Val Cys Ser Ala Met Ser Xaa Ile Cys 1
5 10 1516415PRTConus
musicusSITE(4)..(12)Xaa at residues 4 and 12 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa at residue 6 is Pro or
hydroxy-Pro. 164Gly Cys Cys Xaa Asn Xaa Xaa Cys Gly Ala Ser Xaa Thr Xaa
Cys 1 5 10
1516515PRTConus omariaSITE(5)..(13)Xaa at residue 5 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr; Xaa at residues 6, 7 and 13 is Pro or hydroxy-Pro. 165Gly
Cys Cys Ser Xaa Xaa Xaa Cys Phe Ala Thr Asn Xaa Asp Cys 1
5 10 1516617PRTConus
radiatusSITE(6)..(14)Xaa at residue 6 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr; Xaa at residues 7, 8 and 14 is Pro or hydroxy-Pro. 166Gly
Gly Cys Cys Ser Xaa Xaa Xaa Cys Ile Ala Asn Asn Xaa Leu Cys 1
5 10 15 Ala
16717PRTConus
radiatusSITE(6)..(14)Xaa at residue 6 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr; Xaa at residues 7, 8 and 14 is Pro or hydroxy-Pro. 167Gly
Gly Cys Cys Ser Xaa Xaa Xaa Cys Ile Ala Asn Asn Xaa Phe Cys 1
5 10 15 Ala
16816PRTConus
virgoSITE(6)..(13)Xaa at residues 6, 7 and 13 is Pro or hydroxy-Pro.
168Asp Cys Cys Ser Asn Xaa Xaa Cys Ser Gln Asn Asn Xaa Asp Cys Met 1
5 10 15 16916PRTConus
virgoSITE(6)..(13)Xaa at residues 6, 7 and 13 is Pro or hydroxy-Pro.
169Asp Cys Cys Ser Asn Xaa Xaa Cys Ala His Asn Asn Xaa Asp Cys Arg 1
5 10 15 17020PRTConus
achatinusSITE(1)..(14)Xaa at residues 1, 11 and 14 is Glu or
gamma-carboxy-Glu; Xaa at residue 6 is Pro or hydroxy-Pro. 170Xaa
Cys Cys Thr Asn Xaa Val Cys His Ala Xaa His Gln Xaa Leu Cys 1
5 10 15 Ala Arg Arg Arg
2017116PRTConus
achatinusSITE(6)..(10)Xaa at residue 6 is Pro or hydroxy-Pro; Xaa at
residue 11 is Glu or gamma-carboxy-Glu. 171Gly Cys Cys Ser Asn Xaa Val
Cys His Leu Xaa His Ser Asn Leu Cys 1 5
10 15 17220PRTConus achatinusSITE(1)..(14)Xaa at
residues 1, 11 and 14 is Glu or gamma-carboxy-Glu; Xaa at residue 6
is Pro or hydroxy-Pro. 172Xaa Cys Cys Thr Asn Xaa Val Cys His Val
Xaa His Gln Xaa Leu Cys 1 5 10
15 Ala Arg Arg Arg
2017317PRTConus ammiralisSITE(1)..(15)Xaa at residue 1 is
Gln or pyro-Glu; Xaa at residues 2 and 15 is Glu or
gamma-carboxy-Glu; Xaa at residue 6 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or 173Xaa Xaa Cys Cys Ser
Xaa Xaa Ala Cys Asn Leu Asp His Xaa Xaa Leu 1 5
10 15 Cys
17418PRTConus ammiralisSITE(1)..(15)Xaa at
residues 1, 7 and 14 is Pro or hydroxy-Pro; Xaa at residues 2
and 15 is Glu or gamma-carboxy-Glu. 174Xaa Xaa Cys Cys Ser Asp Xaa
Arg Cys Asn Ser Thr His Xaa Xaa Leu 1 5
10 15 Cys Gly
17521PRTConus arenatusSITE(7)..(12)Xaa at residues 7 and
8 is Pro or hydroxy-Pro; Xaa at residue 10 is Trp (D or L) or
halo-Trp; Xaa at residues 11 and 12 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys. 175Leu Asn Cys Cys Met Ile Xaa
Xaa Cys Xaa Xaa Xaa Xaa Gly Asp Arg 1 5
10 15 Cys Ser Xaa Val Arg
20 17622PRTConus arenatusSITE(9)..(20)Xaa
at residue 9 is Pro or hydroxy-Pro; Xaa at residues 12 and 20
is Glu or gamma-carboxy-Glu; Xaa at residue 14 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or 176Ala
Phe Gly Cys Cys Asp Leu Ile Xaa Cys Leu Xaa Arg Xaa Gly Asn 1
5 10 15 Arg Cys Asn Xaa Val His
20
17721PRTConus arenatusSITE(8)..(16)Xaa at residue 8 is Pro or
hydroxy-Pro; Xaa at residue 10 is Trp (D or L) or halo-Trp; Xaa at
residues 12 and 16 is Lys, N-methyl-Lys, N,N-dimethyl-Lys or
N,N,N-trimethyl-Lys. 177Leu Gly Cys Cys Asn Val Thr Xaa Cys Xaa Xaa Xaa
Xaa Gly Asp Xaa 1 5 10
15 Cys Asn Xaa Val Arg
20 17820PRTConus arenatusSITE(2)..(14)Xaa at residue 2 is Glu
or gamma-carboxy-Glu; Xaa at residues 7 and 14 is Pro or
hydroxy-Pro. 178Asp Xaa Cys Cys Ser Asn Xaa Ala Cys Arg Val Asn Asn Xaa
His Val 1 5 10 15
Cys Arg Arg Arg
2017921PRTConus arenatusSITE(7)..(13)Xaa at residue 7 is Pro or
hydroxy-Pro; Xaa at residue 10 is Trp (D or L) or halo-Trp; Xaa at
residue 12 is Glu or gamma-carboxy-Glu; Xaa at residue 13 is Tyr,
nor-Tyr, mono-halo-Tyr, 179Leu Asn Cys Cys Ser Ile Xaa Gly Cys Xaa Asn
Xaa Xaa Xaa Asp Arg 1 5 10
15 Cys Ser Xaa Val Arg
20 18018PRTConus aurisiacusSITE(7)..(14)Xaa at residues 7
and 14 is Pro or hydroxy-Pro; Xaa at residue 10 is Tyr,
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr. 180Gly Gly Cys Cys Ser His Xaa Val Cys Xaa Phe Asn Asn Xaa Gln
Met 1 5 10 15 Cys
Arg
18118PRTConus aurisiacusSITE(7)..(14)Xaa at residues 7 and 14 is Pro or
hydroxy-Pro. 181Gly Gly Cys Cys Ser His Xaa Val Cys Asn Leu Asn Asn
Xaa Gln Met 1 5 10 15
Cys Arg
18217PRTConus bandanusSITE(6)..(15)Xaa at residues 6 and 7 is Pro or
hydroxy-Pro; Xaa at residues 9 and 15 is Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr. 182Gly Cys
Cys Ser His Xaa Xaa Cys Xaa Ala Asn Asn Gln Ala Xaa Cys 1
5 10 15 Asn
18317PRTConus
betulinusSITE(7)..(15)Xaa at residues 7 and 14 is Pro and
hydroxy-Pro; Xaa at residue 15 is Glu or gamma-carboxy-Glu. 183Gly
Gly Cys Cys Ser His Xaa Ala Cys Ser Val Thr His Xaa Xaa Leu 1
5 10 15 Cys
18418PRTConus
betulinusSITE(6)..(12)Xaa at residue 6 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr; Xaa at residue 7 is Pro and hydroxy-Pro; Xaa at residue
12 is Glu or 184Gly Gly Cys Cys Ser Xaa Xaa Ala Cys Ser Val Xaa His Gln
Asp Leu 1 5 10 15
Cys Asp
18525PRTConus caracteristicusSITE(8)..(22)Xaa at residues 8 and 22 is Pro
or hydroxy-Pro; Xaa at residue 10 is Trp (D or L) or halo-Trp; Xaa
at residue 13 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr,
O-sulpho-Tyr, O-phospho-Tyr or 185Val Ser Cys Cys Val Val Arg Xaa Cys Xaa
Ile Arg Xaa Gln Xaa Xaa 1 5 10
15 Cys Leu Xaa Ala Asp Xaa Arg Thr Leu
20 2518621PRTConus
caracteristicusSITE(1)..(19)Xaa at residue 1 is Gln or pyro-Glu; Xaa at
residue 7 is Pro or hydroxy-Pro; Xaa at residue 10 is Trp (D or
L) or halo-Trp; Xaa at residues 11 and 19 is Glu or
gamma-carboxy-Glu. 186Xaa Asn Cys Cys Ser Ile Xaa Gly Cys Xaa Xaa Xaa Xaa
Gly Asp Xaa 1 5 10 15
Cys Ser Xaa Val Arg
20 18716PRTConus catusSITE(6)..(13)Xaa at residues 6 and 13 is Pro
or hydroxy-Pro; Xaa at residue 11 is Glu or gamma-carboxy-Glu.
187Gly Cys Cys Ser Asn Xaa Val Cys His Leu Xaa His Xaa Asn Ala Cys 1
5 10 15 18817PRTConus
catusSITE(6)..(13)Xaa at residues 6 and 13 is Pro or hydroxy-Pro;
Xaa at residue 9 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr,
O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr. 188Gly Cys Cys Ser Asn Xaa
Ile Cys Xaa Phe Asn Asn Xaa Arg Ile Cys 1 5
10 15 Arg
18917PRTConus episcopatusSITE(1)..(14)Xaa at residues
1 and 14 is Glu or gamma-carboxy-Glu; Xaa at residues 6, 7 and 13 is
Pro or hydroxy-Pro; Xaa at residue 10 is Trp (D or L) or
halo-Trp. 189Xaa Cys Cys Ser Gln Xaa Xaa Cys Arg Xaa Xaa His Xaa Xaa Leu
Cys 1 5 10 15 Ser
19016PRTConus
geographusSITE(6)Xaa at residue 6 is Pro or hydroxy-Pro. 190Gly Cys Cys
Ser His Xaa Ala Cys Ala Gly Asn Asn Gln His Ile Cys 1 5
10 15 19118PRTConus
geographusSITE(6)..(13)Xaa at residues 6 and 13 is Pro or hydroxy-Pro.
191Gly Cys Cys Ala Val Xaa Ser Cys Arg Leu Arg Asn Xaa Asp Leu Cys 1
5 10 15 Gly Gly
19216PRTConus
imperialisNP_BIND(6)..(13)Xaa at residues 6 and 13 is Pro or hydroxy-Pro.
192Gly Cys Cys Ser His Xaa Ala Cys Asn Val Asn Asn Xaa His Ile Cys 1
5 10 15 19320PRTConus
lividusSITE(2)..(10)Xaa at residues 2, 7, 9 and 10 is Pro or
hydroxy-Pro; Xaa at residues 3 and 4 is Glu or gamma-carboxy-Glu.
193Thr Xaa Xaa Xaa Cys Cys Xaa Asn Xaa Xaa Cys Phe Ala Thr Asn Ser 1
5 10 15 Asp Ile Cys Gly
2019417PRTConus lividusSITE(7)..(12)Xaa at residue 7 is Pro or
hydroxy-Pro; Xaa at residue 12 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys. 194Asp Ala Cys Cys Ser Asp
Xaa Arg Cys Ser Gly Xaa His Gln Asp Leu 1 5
10 15 Cys
19517PRTConus lividusSITE(1)..(7)Xaa at residue 1 is
Glu or gamma-carboxy-Glu; Xaa at residue 7 is Pro or
hydroxy-Pro. 195Xaa Asp Cys Cys Ser Asp Xaa Arg Cys Ser Val Gly His Gln
Asp Leu 1 5 10 15
Cys
19616PRTConus lividusSITE(6)Xaa at residue 6 is Pro or hydroxy-Pro.
196Gly Cys Cys Ser His Xaa Ala Cys Ala Gly Ser Asn Ala His Ile Cys 1
5 10 15 19717PRTConus
lividusSITE(1)..(7)Xaa at residue 1 is Glu or gamma-carboxy-Glu; Xaa
at residue 7 is Pro or hydroxy-Pro. 197Xaa Asp Cys Cys Ser Asp Xaa
Arg Cys Ser Val Gly His Gln Asp Met 1 5
10 15 Cys
19816PRTConus lividusSITE(6)..(13)Xaa at residues 6 and
13 is Pro or hydroxy-Pro. 198Gly Cys Cys Ser His Xaa Ala Cys Ala Gly Asn
Asn Xaa His Ile Cys 1 5 10
15 19917PRTConus lividusSITE(6)..(14)Xaa at residues 6 and 13 is
Pro or hydroxy-Pro; Xaa at residue 14 is Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr. 199Gly Cys
Cys Gly Asn Xaa Ser Cys Ser Ile His Ile Xaa Xaa Val Cys 1
5 10 15 Asn
20021PRTConus lividusSITE(4)..(5)Xaa
at residues 4 and 5 is Glu or gamma-carboxy-Glu. 200Thr Asp Ser Xaa
Xaa Cys Cys Leu Asp Ser Arg Cys Ala Gly Gln His 1 5
10 15 Gln Asp Leu Cys Gly
20 20117PRTConus
marmoreusSITE(6)..(15)Xaa at residues 6 and 7 is Pro or hydroxy-Pro;
Xaa at residues 9 and 15 is Tyr, mono-halo-Tyr, di-halo-Tyr,
O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr. 201Gly Cys Cys Ser Asn Xaa
Xaa Cys Xaa Ala Asn Asn Gln Ala Xaa Cys 1 5
10 15 Asn
20216PRTConus marmoreusSITE(6)..(13)Xaa at residues 6
and 13 is Pro or hydroxy-Pro. 202Gly Cys Cys Ser His Xaa Ala Cys Ser Val
Asn Asn Xaa Asp Ile Cys 1 5 10
15 20318PRTConus musicusSITE(2)..(15)Xaa at residues 2 and 12
is Lys, N-methyl-Lys, N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa
at residue 14 is Pro or hydroxy-Pro. 203Gly Xaa Cys Cys Ile Asn Asp
Ala Cys Arg Ser Xaa His Xaa Gln Xaa 1 5
10 15 Cys Ser
20417PRTConus musicusSITE(4)..(15)Xaa at residues 4 and
15 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr,
O-phospho-Tyr or nitro-Tyr; Xaa at residue 13 is Pro or hydroxy-Pro.
204Gly Cys Cys Xaa Asn Ile Ala Cys Arg Ile Asn Asn Xaa Arg Xaa Cys 1
5 10 15 Arg
20517PRTConus
obscurusSITE(6)..(15)Xaa at residues 6 and 13 is Pro or hydroxy-Pro;
Xaa at residues 12 and 15 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr. 205Gly Cys
Cys Ser His Xaa Val Cys Arg Phe Asn Xaa Xaa Xaa Xaa Cys 1
5 10 15 Gly
20618PRTConus
obscurusSITE(2)..(15)Xaa at residue 2 is Glu or gamma-carboxy-Glu;
Xaa at residues 7, 8 and 14 is Pro or hydroxy-Pro; Xaa at
residue 15 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr,
O-sulpho-Tyr, O-phospho-Tyr or 206Asp Xaa Cys Cys Ala Ser Xaa Xaa Cys Arg
Leu Asn Asn Xaa Xaa Val 1 5 10
15 Cys His
20719PRTConus obscurusSITE(6)..(18)Xaa at residue 6 is Pro or
hydroxy-Pro; Xaa at residue 9 is Trp (D or L) or halo-Trp; Xaa at
residues 14 and 18 is Glu or gamma-carboxy-Glu. 207Gly Cys Cys Ser Asn
Xaa Val Cys Xaa Gln Asn Asn Ala Xaa Xaa Cys 1 5
10 15 Arg Xaa Ser
20816PRTConus obscurusSITE(6)..(15)Xaa at
residues 6 and 7 is Pro or hydroxy-Pro; Xaa at residue 15 is
Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr,
O-phospho-Tyr or nitro-Tyr. 208Gly Cys Cys Ser His Xaa Xaa Cys Ala
Gln Asn Asn Gln Asp Xaa Cys 1 5 10
15 20919PRTConus obscurusSITE(6)..(15)Xaa at residue 6 is
Pro or hydroxy-Pro; Xaa at residues 14 and 18 is Glu or
gamma-carboxy-Glu; Xaa at residue 15 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or 209Gly Cys Cys Ser His
Xaa Ala Cys Ser Gly Asn Asn Arg Xaa Xaa Cys 1 5
10 15 Arg Xaa Ser
21018PRTConus omariaSITE(2)..(15)Xaa at residues
2, 7 and 14 is Pro or hydroxy-Pro; Xaa at residue 6 is Tyr,
nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr; Xaa at residue 15 is Glu or 210Asp Xaa Cys Cys Ser Xaa Xaa
Asp Cys Gly Ala Asn His Xaa Xaa Ile 1 5
10 15 Cys Gly
21117PRTConus omariaSITE(1)..(14)Xaa at residues 1 and
14 is Glu or gamma-carboxy-Glu; Xaa at residues 6, 7 and 13 is
Pro or hydroxy-Pro; Xaa at residue 10 is Trp (D or L) or halo-Trp.
211Xaa Cys Cys Ser Gln Xaa Xaa Cys Arg Xaa Xaa His Xaa Xaa Leu Cys 1
5 10 15 Ser
21216PRTConus
omariaSITE(6)..(13)Xaa at residues 6 and 13 is Pro or hydroxy-Pro. 212Gly
Cys Cys Ser His Xaa Ala Cys Ala Gly Asn Asn Xaa His Ile Cys 1
5 10 15 21316PRTConus
omariaSITE(6)..(15)Xaa at residues 6 and 13 is Pro or hydroxy-Pro;
Xaa at residue 15 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr,
O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr. 213Gly Cys Cys Ser Asp Xaa
Ser Cys Asn Val Asn Asn Xaa Asp Xaa Cys 1 5
10 15 21418PRTConus omariaSITE(1)..(7)Xaa at
residues 1 and 2 is Glu or gamma-carboxy-Glu; Xaa at residue 7 is
Pro or hydroxy-Pro. 214Xaa Xaa Cys Cys Ser Asp Xaa Arg Cys Ser Val
Gly His Gln Asp Met 1 5 10
15 Cys Arg
21517PRTConus purpurascensSITE(7)..(15)Xaa at residue 7 is Pro or
hydroxy-Pro; Xaa at residue 15 is Glu or gamma-carboxy-Glu. 215Gly
Gly Cys Cys Ser Asn Xaa Ala Cys Leu Val Asn His Leu Xaa Met 1
5 10 15 Cys
21618PRTConus
purpurascensSITE(3)..(15)Xaa at residues 3, 8 and 15 is Pro or
hydroxy-Pro. 216Arg Asp Xaa Cys Cys Phe Asn Xaa Ala Cys Asn Val Asn Asn
Xaa Gln 1 5 10 15
Ile Cys
21721PRTConus purpurascensSITE(5)..(8)Xaa at residue 5 is Pro or
hydroxy-Pro; Xaa at residue 8 is Trp (D or L) or halo-Trp. 217Cys
Cys Ser Asp Xaa Ser Cys Xaa Arg Leu His Ser Leu Ala Cys Thr 1
5 10 15 Gly Ile Val Asn Arg
20 21816PRTConus
purpurascensSITE(5)Xaa at residue 5 is Pro or hydroxy-Pro. 218Cys Cys Thr
Asn Xaa Ala Cys Leu Val Asn Asn Ile Arg Phe Cys Gly 1 5
10 15 21918PRTConus
regiusSITE(2)..(7)Xaa at residue 2 is Glu or gamma-carboxy-Glu; Xaa
at residue 7 is Pro or hydroxy-Pro. 219Asp Xaa Cys Cys Ser Asp Xaa
Arg Cys His Gly Asn Asn Arg Asp His 1 5
10 15 Cys Ala
22017PRTConus regiusSITE(6)..(13)Xaa at residues 6 and
13 is Pro or hydroxy-Pro. 220Asp Cys Cys Ser His Xaa Leu Cys Arg Leu Phe
Val Xaa Gly Leu Cys 1 5 10
15 Ile
22117PRTConus regiusSITE(6)..(13)Xaa at residues 6 and 13 is Pro or
hydroxy-Pro; Xaa at residue 9 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys. 221Gly Cys Cys Ser His Xaa Val
Cys Xaa Val Arg Xaa Xaa Asp Leu Cys 1 5
10 15 Arg
22216PRTConus regiusSITE(6)..(13)Xaa at residues 6 and
13 is Pro or hydroxy-Pro. 222Gly Cys Cys Ser His Xaa Ala Cys Asn Val Asn
Asn Xaa His Ile Cys 1 5 10
15 22316PRTConus regiusSITE(6)..(12)Xaa at residue 6 is Pro or
hydroxy-Pro; Xaa at residue 12 is Tyr, nor-Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr. 223Gly Cys Cys Ser His Xaa Val Cys Xaa Val Arg Xaa Ser Asp Met
Cys 1 5 10 15
22417PRTConus stercusmuscarumSITE(7)..(14)Xaa at residues 7 and 14 is Pro
or hydroxy-Pro; Xaa at residue 10 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys. 224Gly Gly Cys Cys Ser His Xaa
Ala Cys Xaa Val His Phe Xaa His Ser 1 5
10 15 Cys
22520PRTConus stercusmuscarumSITE(6)..(14)Xaa at
residues 6 and 13 is Pro or hydroxy-Pro; Xaa at residue 14 is Glu or
gamma-carboxy-Glu. 225Val Cys Cys Ser Asn Xaa Val Cys His Val Asp His Xaa
Xaa Leu Cys 1 5 10 15
Arg Arg Arg Arg
2022617PRTConus striatusSITE(6)..(13)Xaa at residues 6 and 13 is Pro
or hydroxy-Pro. 226Gly Cys Cys Ser His Xaa Val Cys Asn Leu Ser Asn Xaa
Gln Ile Cys 1 5 10 15
Arg
22718PRTConus textileSITE(1)..(15)Xaa at residue 1 is Gln or pyro-Glu;
Xaa at residues 2 and 15 is Glu or gamma-carboxy-Glu; Xaa at
residues 7 and 14 is Pro or hydroxy-Pro. 227Xaa Xaa Cys Cys Ser His Xaa
Ala Cys Asn Val Asp His Xaa Xaa Ile 1 5
10 15 Cys Arg
22817PRTConus tulipaSITE(6)Xaa at residue 6 is Pro or
hydroxy-Pro. 228Gly Cys Cys Ser Asn Xaa Ala Cys Leu Val Asn His Ile Arg
Phe Cys 1 5 10 15
Gly
22917PRTConus virgoSITE(6)..(13)Xaa at residues 6 and 13 is Pro or
hydroxy-Pro. 229Asp Cys Cys Asp Asp Xaa Ala Cys Thr Val Asn Asn Xaa Gly
Leu Cys 1 5 10 15
Thr
23020PRTConus textileSITE(6)..(13)Xaa at residues 6, 7 and 13 is Pro or
hydroxy-Pro; Xaa at residue 11 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys. 230Gly Cys Cys Ser Asn Xaa Xaa
Cys Ile Ala Xaa Asn Xaa His Met Cys 1 5
10 15 Gly Gly Arg Arg
2023118PRTConus geographusSITE(5)..(9)Xaa at
residue 5 is Pro or hydroxy-Pro; Xaa at residue 8 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr; Xaa at residue 9 is Glu or 231Cys Cys Thr Ile Xaa Ser Cys Xaa
Xaa Xaa Xaa Xaa Ile Xaa Ala Cys 1 5 10
15 Val Phe
23218PRTConus regiusSITE(6)..(16)Xaa at residues 6 and 16 is
Pro or hydroxy-Pro; Xaa at residue 13 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys. 232Gly Cys Cys Gly Asn Xaa Ala
Cys Ser Gly Ser Ser Xaa Asp Ala Xaa 1 5
10 15 Ser Cys
233108DNAConus imperialisCDS(1)..(105) 233tct gat gga
aag agt gcc gcg gcc aaa gcc aaa ccg tct cac ctg acg 48Ser Asp Gly
Lys Ser Ala Ala Ala Lys Ala Lys Pro Ser His Leu Thr1 5
10 15 gct cca ttc atc agg gac gaa tgc
tgt tcc gat tct cgc tgt ggc aag 96Ala Pro Phe Ile Arg Asp Glu Cys
Cys Ser Asp Ser Arg Cys Gly Lys 20 25
30 aac tgt ctt tga
108Asn Cys Leu 35 23435PRTConus imperialis
234Ser Asp Gly Lys Ser Ala Ala Ala Lys Ala Lys Pro Ser His Leu Thr 1
5 10 15 Ala Pro Phe Ile
Arg Asp Glu Cys Cys Ser Asp Ser Arg Cys Gly Lys 20
25 30 Asn Cys Leu
35
235108DNAConus imperialisCDS(1)..(105) 235ttt gat gga
agg aat gcc cca gcc gac gac aaa gcg tct gac ctg atc 48Phe Asp Gly
Arg Asn Ala Pro Ala Asp Asp Lys Ala Ser Asp Leu Ile1 5
10 15 gct caa atc gtc agg aga gca tgc
tgt tcc gat cgt cgc tgt aga tgg 96Ala Gln Ile Val Arg Arg Ala Cys
Cys Ser Asp Arg Arg Cys Arg Trp 20 25
30 agg tgt ggt tga
108Arg Cys Gly 35 23635PRTConus imperialis
236Phe Asp Gly Arg Asn Ala Pro Ala Asp Asp Lys Ala Ser Asp Leu Ile 1
5 10 15 Ala Gln Ile Val
Arg Arg Ala Cys Cys Ser Asp Arg Arg Cys Arg Trp 20
25 30 Arg Cys Gly
35
237145DNAConus regiusCDS(1)..(105) 237tct gat gga agg
aat gcc gca gcc gac gcc aga gcg tct ccc cgg atc 48Ser Asp Gly Arg
Asn Ala Ala Ala Asp Ala Arg Ala Ser Pro Arg Ile1 5
10 15 gct ctt ttc ctc agg ttc aca tgc tgt
agg aga ggt acc tgt tcc cag 96Ala Leu Phe Leu Arg Phe Thr Cys Cys
Arg Arg Gly Thr Cys Ser Gln 20 25
30 cac tgt ggt tgaagacact gctgctccag gaccctctga accacgacgt
145His Cys Gly
35 23835PRTConus regius
238Ser Asp Gly Arg Asn Ala Ala Ala Asp Ala Arg Ala Ser Pro Arg Ile 1
5 10 15 Ala Leu Phe Leu
Arg Phe Thr Cys Cys Arg Arg Gly Thr Cys Ser Gln 20
25 30 His Cys Gly
35
239145DNAConus regiusCDS(1)..(105) 239tct aat gga agg
aat gcc gca gcc gac gcc aaa gcg tct caa cgg atc 48Ser Asn Gly Arg
Asn Ala Ala Ala Asp Ala Lys Ala Ser Gln Arg Ile1 5
10 15 gct cca ttc ctc agg gac tat tgc tgt
agg aga cat gcc tgt acg ttg 96Ala Pro Phe Leu Arg Asp Tyr Cys Cys
Arg Arg His Ala Cys Thr Leu 20 25
30 att tgt ggt tgaagacgct gctgctccag gaccctctga accacgacgt
145Ile Cys Gly
35 24035PRTConus regius
240Ser Asn Gly Arg Asn Ala Ala Ala Asp Ala Lys Ala Ser Gln Arg Ile 1
5 10 15 Ala Pro Phe Leu
Arg Asp Tyr Cys Cys Arg Arg His Ala Cys Thr Leu 20
25 30 Ile Cys Gly
35
241145DNAConus regiusCDS(1)..(105) 241tct aat gga agg
aat gcc gca gcc gac gcc aaa gcg tct caa cgg atc 48Ser Asn Gly Arg
Asn Ala Ala Ala Asp Ala Lys Ala Ser Gln Arg Ile1 5
10 15 gct cca ttc ctc agg gac tat tgc tgt
agg aga cct ccc tgt acg ttg 96Ala Pro Phe Leu Arg Asp Tyr Cys Cys
Arg Arg Pro Pro Cys Thr Leu 20 25
30 att tgt ggt tgaagacgct gctgctccag gaccctctga accacgacgt
145Ile Cys Gly
35 24235PRTConus regius
242Ser Asn Gly Arg Asn Ala Ala Ala Asp Ala Lys Ala Ser Gln Arg Ile 1
5 10 15 Ala Pro Phe Leu
Arg Asp Tyr Cys Cys Arg Arg Pro Pro Cys Thr Leu 20
25 30 Ile Cys Gly
35
243136DNAConus regiusCDS(1)..(96) 243tct aat aaa agg
aag aat gcc gca atg ctt gac atg atc gct caa cac 48Ser Asn Lys Arg
Lys Asn Ala Ala Met Leu Asp Met Ile Ala Gln His1 5
10 15 gcc ata agg ggt tgc tgt tcc gat cct
cgc tgt aga tat aga tgt cgt 96Ala Ile Arg Gly Cys Cys Ser Asp Pro
Arg Cys Arg Tyr Arg Cys Arg 20 25
30 tgaagacgct gctgctccag gaccctctga accacgacgt
13624432PRTConus regius 244Ser Asn Lys Arg Lys Asn Ala Ala Met
Leu Asp Met Ile Ala Gln His 1 5 10
15 Ala Ile Arg Gly Cys Cys Ser Asp Pro Arg Cys Arg Tyr
Arg Cys Arg 20 25 30
245145DNAConus regiusCDS(1)..(105) 245ttt aat gga agg agt gcc gca gcc
gac caa aat gcg cct ggc ctg atc 48Phe Asn Gly Arg Ser Ala Ala Ala
Asp Gln Asn Ala Pro Gly Leu Ile1 5 10
15 gct caa gtc gtc aga gga ggg tgc tgt tcc gat ccc cgc
tgc gcc tgg 96Ala Gln Val Val Arg Gly Gly Cys Cys Ser Asp Pro Arg
Cys Ala Trp 20 25 30
aga tgt ggt tgaagacgtt gctgctccag gaccctctga accacgacgt
145Arg Cys Gly 35
24635PRTConus regius 246Phe Asn Gly
Arg Ser Ala Ala Ala Asp Gln Asn Ala Pro Gly Leu Ile 1 5
10 15 Ala Gln Val Val Arg Gly Gly
Cys Cys Ser Asp Pro Arg Cys Ala Trp 20 25
30 Arg Cys Gly
35
247145DNAConus regiusCDS(1)..(105) 247ttt gat gga agg aat gcc gca
gcc gac gcc aaa gtg att aac acg gtc 48Phe Asp Gly Arg Asn Ala Ala
Ala Asp Ala Lys Val Ile Asn Thr Val1 5 10
15 gct cga atc gcc tgg gat ata tgc tgt tcc gaa cct
gac tgt aac cat 96Ala Arg Ile Ala Trp Asp Ile Cys Cys Ser Glu Pro
Asp Cys Asn His 20 25 30
aaa tgt gtt tgaagacgct tctgctccag gaccctctga accacgacgt
145Lys Cys Val 35
24835PRTConus regius 248Phe Asp Gly
Arg Asn Ala Ala Ala Asp Ala Lys Val Ile Asn Thr Val 1 5
10 15 Ala Arg Ile Ala Trp Asp Ile
Cys Cys Ser Glu Pro Asp Cys Asn His 20 25
30 Lys Cys Val
35
249136DNAConus regiusCDS(1)..(96) 249tct aat aaa agg aag aat gcc
gca atg ctt gac atg atc gct caa cac 48Ser Asn Lys Arg Lys Asn Ala
Ala Met Leu Asp Met Ile Ala Gln His1 5 10
15 gcc ata agg ggt tgc tgt tcc gat cct cgc tgt aaa
cat cag tgt ggt 96Ala Ile Arg Gly Cys Cys Ser Asp Pro Arg Cys Lys
His Gln Cys Gly 20 25 30
tgaagacgct gctgctccag gaccctctga accacgacgt
13625032PRTConus regius 250Ser Asn Lys Arg Lys Asn Ala Ala Met Leu Asp
Met Ile Ala Gln His 1 5 10
15 Ala Ile Arg Gly Cys Cys Ser Asp Pro Arg Cys Lys His Gln Cys
Gly 20 25 30
251136DNAConus musicusCDS(1)..(105) 251atc aag aat aca gca gcc agc aac
aaa gcg tct agc ctg gtg gct ctt 48Ile Lys Asn Thr Ala Ala Ser Asn
Lys Ala Ser Ser Leu Val Ala Leu1 5 10
15 gtt gtc agg gga tgc tgt tac aat cct gtc tgc aag aaa
tat tat tgt 96Val Val Arg Gly Cys Cys Tyr Asn Pro Val Cys Lys Lys
Tyr Tyr Cys 20 25 30
tgg aaa ggc tgatgctcca ggaccctctg aaccacgacg t
136Trp Lys Gly 35
25235PRTConus musicus 252Ile Lys Asn Thr Ala Ala Ser
Asn Lys Ala Ser Ser Leu Val Ala Leu 1 5
10 15 Val Val Arg Gly Cys Cys Tyr Asn Pro Val Cys
Lys Lys Tyr Tyr Cys 20 25
30 Trp Lys Gly
35
253148DNAConus purpurascensCDS(1)..(117) 253tct gaa ggc agg aat gct gaa
gcc atc gac aac gcc tta gac cag agg 48Ser Glu Gly Arg Asn Ala Glu
Ala Ile Asp Asn Ala Leu Asp Gln Arg1 5 10
15 gat cca aag cga cag gag ccg ggg tgc tgt agg cat
cct gcc tgt ggg 96Asp Pro Lys Arg Gln Glu Pro Gly Cys Cys Arg His
Pro Ala Cys Gly 20 25 30
aag aac aga tgt gga aga cgc tgatgctcca ggaccctctg aaccacgacg t
148Lys Asn Arg Cys Gly Arg Arg
35 25439PRTConus
purpurascens 254Ser Glu Gly Arg Asn Ala Glu Ala Ile Asp Asn Ala Leu Asp
Gln Arg 1 5 10 15
Asp Pro Lys Arg Gln Glu Pro Gly Cys Cys Arg His Pro Ala Cys Gly
20 25 30 Lys Asn Arg Cys
Gly Arg Arg 35
255156DNAConus
musicusCDS(1)..(102) 255tct gat ggc agg aat att gca gtc gac gac aga tgg
tct ttc tat acg 48Ser Asp Gly Arg Asn Ile Ala Val Asp Asp Arg Trp
Ser Phe Tyr Thr1 5 10 15
ctc ttc cat gct act tgc tgt gcc gat cct gac tgt aga ttc cgg ccc
96Leu Phe His Ala Thr Cys Cys Ala Asp Pro Asp Cys Arg Phe Arg Pro
20 25 30 ggt tgt tgatctttgt
tcttcaaaga cgctgctggc ccaggaccct ctgaaccacg 152Gly Cys
acgt
15625634PRTConus musicus 256Ser Asp
Gly Arg Asn Ile Ala Val Asp Asp Arg Trp Ser Phe Tyr Thr 1
5 10 15 Leu Phe His Ala Thr Cys
Cys Ala Asp Pro Asp Cys Arg Phe Arg Pro 20
25 30 Gly Cys
257142DNAConus musicusCDS(1)..(102) 257atc aag aat
act gca gcc agc aac aaa gcg cct agc ctg gtg gct att 48Ile Lys Asn
Thr Ala Ala Ser Asn Lys Ala Pro Ser Leu Val Ala Ile1 5
10 15 gcc gtc agg gga tgc tgt tac aat
cct tcc tgt tgg ccg aaa aca tat 96Ala Val Arg Gly Cys Cys Tyr Asn
Pro Ser Cys Trp Pro Lys Thr Tyr 20 25
30 tgt agt tggaaaggct gatgctccag gaccctctga accacgacgt
142Cys Ser
25834PRTConus musicus 258Ile Lys Asn Thr Ala Ala Ser Asn Lys Ala Pro Ser
Leu Val Ala Ile 1 5 10
15 Ala Val Arg Gly Cys Cys Tyr Asn Pro Ser Cys Trp Pro Lys Thr Tyr
20 25 30 Cys Ser
259161DNAConus
musicusCDS(1)..(108) 259tct gat agc agg aat gtc gca atc gag gac aga gtg
tct gac ctg cac 48Ser Asp Ser Arg Asn Val Ala Ile Glu Asp Arg Val
Ser Asp Leu His1 5 10 15
tct atg ttc ttc gat gtt tct tgc tgt agc aat cct acc tgt aaa gaa
96Ser Met Phe Phe Asp Val Ser Cys Cys Ser Asn Pro Thr Cys Lys Glu
20 25 30 acg tat ggt tgt
tgatcgttgg ttttgaagac gctgatgctc caggaccctc 148Thr Tyr Gly Cys
35
tgaaccacga cgt
16126036PRTConus musicus 260Ser Asp Ser Arg Asn Val
Ala Ile Glu Asp Arg Val Ser Asp Leu His 1 5
10 15 Ser Met Phe Phe Asp Val Ser Cys Cys Ser
Asn Pro Thr Cys Lys Glu 20 25
30 Thr Tyr Gly Cys
35
261156DNAConus musicusCDS(1)..(102) 261tct gtt ggc agg aat att gca gtc
gac gac aga ggg att ttc tct acg 48Ser Val Gly Arg Asn Ile Ala Val
Asp Asp Arg Gly Ile Phe Ser Thr1 5 10
15 ctc ttc cat gct cat tgc tgt gcc aat ccc atc tgt aaa
aac acg ccc 96Leu Phe His Ala His Cys Cys Ala Asn Pro Ile Cys Lys
Asn Thr Pro 20 25 30
ggt tgt tgatctttgt tcttcaaaga cgctgctggc ccaggaccct ctgaaccacg
152Gly Cys acgt
15626234PRTConus musicus 262Ser Val Gly Arg Asn Ile Ala Val Asp Asp Arg
Gly Ile Phe Ser Thr 1 5 10
15 Leu Phe His Ala His Cys Cys Ala Asn Pro Ile Cys Lys Asn Thr
Pro 20 25 30 Gly
Cys
263161DNAConus musicusCDS(1)..(108) 263tcc gat ggc agg aat gtc gca atc
gac gac aga gtg tct gac ctg cac 48Ser Asp Gly Arg Asn Val Ala Ile
Asp Asp Arg Val Ser Asp Leu His1 5 10
15 tct atg ttc ttc gat att gct tgc tgt aac aat cct acc
tgt aaa gaa 96Ser Met Phe Phe Asp Ile Ala Cys Cys Asn Asn Pro Thr
Cys Lys Glu 20 25 30
acg tat ggt tgt tgatcgttgg ttttgaagac gctgatgctc caggaccctc
148Thr Tyr Gly Cys 35
tgaaccacga cgt
16126436PRTConus musicus 264Ser
Asp Gly Arg Asn Val Ala Ile Asp Asp Arg Val Ser Asp Leu His 1
5 10 15 Ser Met Phe Phe Asp
Ile Ala Cys Cys Asn Asn Pro Thr Cys Lys Glu 20
25 30 Thr Tyr Gly Cys
35
265161DNAConus musicusCDS(1)..(108) 265tct gat ggc agg
aat gtc gca atc gag gac aga gtg tct gac ctg ctc 48Ser Asp Gly Arg
Asn Val Ala Ile Glu Asp Arg Val Ser Asp Leu Leu1 5
10 15 tct atg ctc ttc gat gtt gct tgc tgt
agc aat cct gtc tgt aaa gaa 96Ser Met Leu Phe Asp Val Ala Cys Cys
Ser Asn Pro Val Cys Lys Glu 20 25
30 acg tat ggt tgt tgatcgttgg ttttgaagac gctgatgctc
caggaccctc 148Thr Tyr Gly Cys
35
tgaaccacga cgt
16126636PRTConus musicus 266Ser Asp Gly Arg Asn Val Ala Ile Glu Asp Arg
Val Ser Asp Leu Leu 1 5 10
15 Ser Met Leu Phe Asp Val Ala Cys Cys Ser Asn Pro Val Cys Lys
Glu 20 25 30 Thr
Tyr Gly Cys 35
267154DNAConus
betulinusCDS(1)..(123) 267tat gat ggc agg aat gct gcc gcc gac gac aaa gct
ttt gac ctg ctg 48Tyr Asp Gly Arg Asn Ala Ala Ala Asp Asp Lys Ala
Phe Asp Leu Leu1 5 10 15
gct atg acc ata agg gga gga tgc tgt tcc tat cct ccc tgt atc gcg
96Ala Met Thr Ile Arg Gly Gly Cys Cys Ser Tyr Pro Pro Cys Ile Ala
20 25 30 agt aat cct aaa tgt
ggt gga aga cgc tgatgctcca ggaccctctg 143Ser Asn Pro Lys Cys
Gly Gly Arg Arg 35 40
aaccacaacg t
15426841PRTConus betulinus 268Tyr Asp Gly Arg Asn Ala Ala
Ala Asp Asp Lys Ala Phe Asp Leu Leu 1 5
10 15 Ala Met Thr Ile Arg Gly Gly Cys Cys Ser Tyr
Pro Pro Cys Ile Ala 20 25
30 Ser Asn Pro Lys Cys Gly Gly Arg Arg
35 40
269151DNAConus lividusCDS(1)..(111) 269ttt gat ggc agg aat gct gca ggc
aac gcc aaa atg tcc gcc ctg atg 48Phe Asp Gly Arg Asn Ala Ala Gly
Asn Ala Lys Met Ser Ala Leu Met1 5 10
15 gcc ctg acc atc agg gga tgc tgt tcc cat cct gtc tgt
agc gcg atg 96Ala Leu Thr Ile Arg Gly Cys Cys Ser His Pro Val Cys
Ser Ala Met 20 25 30
agt cca atc tgt ggc tgaagacgct gatgccccag gaccctctga accacgacgt
151Ser Pro Ile Cys Gly
35 27037PRTConus
lividus 270Phe Asp Gly Arg Asn Ala Ala Gly Asn Ala Lys Met Ser Ala Leu
Met 1 5 10 15 Ala
Leu Thr Ile Arg Gly Cys Cys Ser His Pro Val Cys Ser Ala Met
20 25 30 Ser Pro Ile Cys Gly
35
271196DNAConus musicusCDS(1)..(165)
271atc aag aat gct gca gct gac gac aaa gca tct gac ctg ctc tct cag
48Ile Lys Asn Ala Ala Ala Asp Asp Lys Ala Ser Asp Leu Leu Ser Gln1
5 10 15 atc gtc agg aat gct
gca tcc aat gac aaa ggg tct gac ctg atg act 96Ile Val Arg Asn Ala
Ala Ser Asn Asp Lys Gly Ser Asp Leu Met Thr 20
25 30 ctt gcc ctc agg gga tgc tgt aaa aat cct
tac tgt ggt gcg tcg aaa 144Leu Ala Leu Arg Gly Cys Cys Lys Asn Pro
Tyr Cys Gly Ala Ser Lys 35 40 45
aca tat tgt ggt aga aga cgc tgatgctcca ggaccctctg aaccacgacg t
196Thr Tyr Cys Gly Arg Arg Arg
50 55 27255PRTConus
musicus 272Ile Lys Asn Ala Ala Ala Asp Asp Lys Ala Ser Asp Leu Leu Ser
Gln 1 5 10 15 Ile
Val Arg Asn Ala Ala Ser Asn Asp Lys Gly Ser Asp Leu Met Thr
20 25 30 Leu Ala Leu Arg Gly
Cys Cys Lys Asn Pro Tyr Cys Gly Ala Ser Lys 35
40 45 Thr Tyr Cys Gly Arg Arg Arg
50 55
273139DNAConus omariaCDS(40)..(108) 273tctgatggca
ggaatgccgc agcgtctgac ctgatggat ctg acc atc aag gga 54
Leu Thr Ile Lys Gly
1 5tgc tgt tct tat cct ccc tgt ttc gcg
act aat cca gac tgt ggt cga 102Cys Cys Ser Tyr Pro Pro Cys Phe Ala
Thr Asn Pro Asp Cys Gly Arg 10 15
20 cga cgc tgatgctcca ggaccctctg aaccacgacg t
139Arg Arg 27423PRTConus
omaria 274Leu Thr Ile Lys Gly Cys Cys Ser Tyr Pro Pro Cys Phe Ala Thr Asn
1 5 10 15 Pro Asp
Cys Gly Arg Arg Arg 20
275126DNAConus
radiatusCDS(1)..(123) 275ttt gat ggc agg aat gcc gca gcc gac tac aaa ggg
tct gaa ttg ctc 48Phe Asp Gly Arg Asn Ala Ala Ala Asp Tyr Lys Gly
Ser Glu Leu Leu1 5 10 15
gct atg acc gtc agg gga gga tgc tgt tcc tat cct ccc tgt atc gca
96Ala Met Thr Val Arg Gly Gly Cys Cys Ser Tyr Pro Pro Cys Ile Ala
20 25 30 aat aat cct ctt tgt
gct gga aga cgc tga 126Asn Asn Pro Leu Cys
Ala Gly Arg Arg 35 40 27641PRTConus
radiatus 276Phe Asp Gly Arg Asn Ala Ala Ala Asp Tyr Lys Gly Ser Glu Leu
Leu 1 5 10 15 Ala
Met Thr Val Arg Gly Gly Cys Cys Ser Tyr Pro Pro Cys Ile Ala
20 25 30 Asn Asn Pro Leu Cys
Ala Gly Arg Arg 35
40 277126DNAConus radiatusCDS(1)..(123)
277ttt gat ggc agg aat gcc gca gcc gac tac aaa ggg tct gaa ttg ctc
48Phe Asp Gly Arg Asn Ala Ala Ala Asp Tyr Lys Gly Ser Glu Leu Leu1
5 10 15 gct atg acc gtc agg
gga gga tgc tgt tcc tat cct ccc tgt atc gca 96Ala Met Thr Val Arg
Gly Gly Cys Cys Ser Tyr Pro Pro Cys Ile Ala 20
25 30 aat aat cct ttt tgt gct gga aga cgc tga
126Asn Asn Pro Phe Cys Ala Gly Arg Arg
35 40 27841PRTConus radiatus 278Phe Asp Gly Arg
Asn Ala Ala Ala Asp Tyr Lys Gly Ser Glu Leu Leu 1 5
10 15 Ala Met Thr Val Arg Gly Gly Cys
Cys Ser Tyr Pro Pro Cys Ile Ala 20 25
30 Asn Asn Pro Phe Cys Ala Gly Arg Arg
35 40
279155DNAConus virgoCDS(1)..(114) 279tct tat gac agg tat gcc tcg ccc
gtc gac aga gcg tct gcc ctg atc 48Ser Tyr Asp Arg Tyr Ala Ser Pro
Val Asp Arg Ala Ser Ala Leu Ile1 5 10
15 gct cag gcc atc ctt cga gat tgc tgt tcc aat cct ccc
tgt tcc caa 96Ala Gln Ala Ile Leu Arg Asp Cys Cys Ser Asn Pro Pro
Cys Ser Gln 20 25 30
aat aat cca gac tgt atg taaagacgct gcttgctcca ggaccctctg
144Asn Asn Pro Asp Cys Met 35
aaccacgacg t
15528038PRTConus virgo 280Ser Tyr Asp
Arg Tyr Ala Ser Pro Val Asp Arg Ala Ser Ala Leu Ile 1 5
10 15 Ala Gln Ala Ile Leu Arg Asp
Cys Cys Ser Asn Pro Pro Cys Ser Gln 20 25
30 Asn Asn Pro Asp Cys Met
35
281155DNAConus virgoCDS(1)..(114) 281tct tat ggc agg tat gcc tca
ccc gtc gac aga gcg tct gcc ctg atc 48Ser Tyr Gly Arg Tyr Ala Ser
Pro Val Asp Arg Ala Ser Ala Leu Ile1 5 10
15 gct cag gcc atc ctt cga gat tgc tgc tcc aat cct
cct tgt gcc cat 96Ala Gln Ala Ile Leu Arg Asp Cys Cys Ser Asn Pro
Pro Cys Ala His 20 25 30
aat aat cca gac tgt cgt taaagacgct gcttgctcca ggaccctctg
144Asn Asn Pro Asp Cys Arg 35
aaccacgacg t
15528238PRTConus virgo 282Ser Tyr Gly
Arg Tyr Ala Ser Pro Val Asp Arg Ala Ser Ala Leu Ile 1 5
10 15 Ala Gln Ala Ile Leu Arg Asp
Cys Cys Ser Asn Pro Pro Cys Ala His 20 25
30 Asn Asn Pro Asp Cys Arg
35
283126DNAConus achatinusCDS(1)..(123) 283tct gat ggc agg aat gcc
gca gcc aac gac aaa gcg tct ggc atg agc 48Ser Asp Gly Arg Asn Ala
Ala Ala Asn Asp Lys Ala Ser Gly Met Ser1 5
10 15 gcg ctg gcc gtc aat gaa tgc tgt acc aac cct
gtc tgt cac gcg gaa 96Ala Leu Ala Val Asn Glu Cys Cys Thr Asn Pro
Val Cys His Ala Glu 20 25 30
cat caa gaa ctt tgt gct aga aga cgc tga
126His Gln Glu Leu Cys Ala Arg Arg Arg 35
40 28441PRTConus achatinus 284Ser Asp Gly Arg Asn Ala Ala Ala Asn
Asp Lys Ala Ser Gly Met Ser 1 5 10
15 Ala Leu Ala Val Asn Glu Cys Cys Thr Asn Pro Val Cys
His Ala Glu 20 25 30
His Gln Glu Leu Cys Ala Arg Arg Arg
35 40 285126DNAConus
achatinusCDS(1)..(123) 285tct gat ggc agg aat gcc gca gcc aac gac aaa gcg
tct gac gtg atc 48Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala
Ser Asp Val Ile1 5 10 15
acg ctg gcc ctc aag gga tgc tgt tcc aac cct gtc tgt cac ttg gag
96Thr Leu Ala Leu Lys Gly Cys Cys Ser Asn Pro Val Cys His Leu Glu
20 25 30 cat tca aac ctt tgt
ggt aga aga cgc tga 126His Ser Asn Leu Cys
Gly Arg Arg Arg 35 40 28641PRTConus
achatinus 286Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Asp Val
Ile 1 5 10 15 Thr
Leu Ala Leu Lys Gly Cys Cys Ser Asn Pro Val Cys His Leu Glu
20 25 30 His Ser Asn Leu Cys
Gly Arg Arg Arg 35
40 287126DNAConus achatinusCDS(1)..(123)
287tct gat ggc agg aat gcc gca gcc aac gac aaa gcg tct ggc atg agc
48Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Gly Met Ser1
5 10 15 gcg ctg gcc gtc aat
gaa tgc tgt acc aac cct gtc tgt cac gtg gaa 96Ala Leu Ala Val Asn
Glu Cys Cys Thr Asn Pro Val Cys His Val Glu 20
25 30 cat caa gaa ctt tgt gct aga aga cgc tga
126His Gln Glu Leu Cys Ala Arg Arg Arg
35 40 28841PRTConus achatinus 288Ser Asp Gly
Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Gly Met Ser 1 5
10 15 Ala Leu Ala Val Asn Glu Cys
Cys Thr Asn Pro Val Cys His Val Glu 20 25
30 His Gln Glu Leu Cys Ala Arg Arg Arg
35 40
289220DNAConus ammiralisCDS(1)..(180) 289atg ttc acc gtg ttt ctg
ttg gtt gtc ttg gca acc acc gtc gtt tcc 48Met Phe Thr Val Phe Leu
Leu Val Val Leu Ala Thr Thr Val Val Ser1 5
10 15 ttc act tca gat cgt gca ttt cgt ggc agg aat
gcc gca gcc aaa gcg 96Phe Thr Ser Asp Arg Ala Phe Arg Gly Arg Asn
Ala Ala Ala Lys Ala 20 25 30
tct ggc ctg gtc ggt ctg acc gac aag agg caa gaa tgc tgt tct tat
144Ser Gly Leu Val Gly Leu Thr Asp Lys Arg Gln Glu Cys Cys Ser Tyr
35 40 45 cct gcc tgt aac
cta gat cat cca gaa ctt tgt ggt tgaagacgct 190Pro Ala Cys Asn
Leu Asp His Pro Glu Leu Cys Gly 50 55
60 gatgctccag gaccctctga accacgacgt
22029060PRTConus ammiralis 290Met Phe Thr Val Phe Leu
Leu Val Val Leu Ala Thr Thr Val Val Ser 1 5
10 15 Phe Thr Ser Asp Arg Ala Phe Arg Gly Arg
Asn Ala Ala Ala Lys Ala 20 25
30 Ser Gly Leu Val Gly Leu Thr Asp Lys Arg Gln Glu Cys Cys
Ser Tyr 35 40 45
Pro Ala Cys Asn Leu Asp His Pro Glu Leu Cys Gly 50
55 60 291223DNAConus
ammiralisCDS(1)..(192) 291atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc
act gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr
Thr Val Val Ser1 5 10 15
tcc act tca ggt cgt cgt gca ttt cgt ggc agg aat gcc gca gcc aaa
96Ser Thr Ser Gly Arg Arg Ala Phe Arg Gly Arg Asn Ala Ala Ala Lys
20 25 30 gcg tct gga ctg gtc
ggt ctg act gac agg aga cca gaa tgc tgt agt 144Ala Ser Gly Leu Val
Gly Leu Thr Asp Arg Arg Pro Glu Cys Cys Ser 35 40
45 gat cct cgc tgt aac tcg act cat cca gaa
ctt tgt ggt gga aga cgc 192Asp Pro Arg Cys Asn Ser Thr His Pro Glu
Leu Cys Gly Gly Arg Arg 50 55 60
tgatgctcca ggaccctctg aaccacgacg t
22329264PRTConus ammiralis 292Met Phe Thr Val Phe Leu Leu Val Val
Leu Ala Thr Thr Val Val Ser 1 5 10
15 Ser Thr Ser Gly Arg Arg Ala Phe Arg Gly Arg Asn Ala
Ala Ala Lys 20 25 30
Ala Ser Gly Leu Val Gly Leu Thr Asp Arg Arg Pro Glu Cys Cys Ser
35 40 45 Asp Pro Arg Cys
Asn Ser Thr His Pro Glu Leu Cys Gly Gly Arg Arg 50
55 60 293151DNAConus
arenatusCDS(1)..(120) 293tct gat ggc agg aat gcc gca gcc aac gcg ttt gac
ctg atc gat ctg 48Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala Phe Asp
Leu Ile Asp Leu1 5 10 15
acc gcc agg cta aat tgc tgt atg att ccc ccc tgt tgg aag aaa tat
96Thr Ala Arg Leu Asn Cys Cys Met Ile Pro Pro Cys Trp Lys Lys Tyr
20 25 30 gga gac aga tgt agt
gaa gta cgc tgatgctcca ggaccctctg aaccacgacg 150Gly Asp Arg Cys Ser
Glu Val Arg 35
40 t
15129440PRTConus arenatus 294Ser Asp Gly
Arg Asn Ala Ala Ala Asn Ala Phe Asp Leu Ile Asp Leu 1 5
10 15 Thr Ala Arg Leu Asn Cys Cys
Met Ile Pro Pro Cys Trp Lys Lys Tyr 20 25
30 Gly Asp Arg Cys Ser Glu Val Arg
35 40
295126DNAConus arenatusCDS(1)..(93) 295tct gat ggc agg aat gcc
gca cgc aaa gcg ttt ggc tgc tgc gac tta 48Ser Asp Gly Arg Asn Ala
Ala Arg Lys Ala Phe Gly Cys Cys Asp Leu1 5
10 15 ata ccc tgt ttg gag aga tat ggt aac aga tgt
aat gaa gtg cac 93Ile Pro Cys Leu Glu Arg Tyr Gly Asn Arg Cys
Asn Glu Val His 20 25 30
tgatgctcca ggaccctctg aaccacgcga cgt
12629631PRTConus arenatus 296Ser Asp Gly Arg Asn Ala Ala Arg Lys Ala Phe
Gly Cys Cys Asp Leu 1 5 10
15 Ile Pro Cys Leu Glu Arg Tyr Gly Asn Arg Cys Asn Glu Val His
20 25 30
297151DNAConus arenatusCDS(1)..(120) 297tct gat ggc agc aat gcc gca gcc
aac gag ttt gac ctg atc gct ctg 48Ser Asp Gly Ser Asn Ala Ala Ala
Asn Glu Phe Asp Leu Ile Ala Leu1 5 10
15 acc gcc agg cta ggt tgc tgt aac gtt aca ccc tgt tgg
gag aaa tat 96Thr Ala Arg Leu Gly Cys Cys Asn Val Thr Pro Cys Trp
Glu Lys Tyr 20 25 30
gga gac aaa tgt aat gaa gta cgc tgatgcttca ggaccctctg aaccacgacg
150Gly Asp Lys Cys Asn Glu Val Arg
35 40 t
15129840PRTConus
arenatus 298Ser Asp Gly Ser Asn Ala Ala Ala Asn Glu Phe Asp Leu Ile Ala
Leu 1 5 10 15 Thr
Ala Arg Leu Gly Cys Cys Asn Val Thr Pro Cys Trp Glu Lys Tyr
20 25 30 Gly Asp Lys Cys Asn
Glu Val Arg 35
40 299148DNAConus arenatusCDS(1)..(117)
299tct gat ggc agg aat gtc gca gca aaa gcg ttt cac cgg atc ggc cgg
48Ser Asp Gly Arg Asn Val Ala Ala Lys Ala Phe His Arg Ile Gly Arg1
5 10 15 acc atc agg gat gaa
tgc tgt tcc aat cct gcc tgt agg gtg aat aat 96Thr Ile Arg Asp Glu
Cys Cys Ser Asn Pro Ala Cys Arg Val Asn Asn 20
25 30 cca cac gtt tgt aga cga cgc tgatgctcca
ggaccctctg aaccacgacg t 148Pro His Val Cys Arg Arg Arg
35
30039PRTConus arenatus 300Ser Asp Gly Arg Asn Val Ala Ala Lys Ala
Phe His Arg Ile Gly Arg 1 5 10
15 Thr Ile Arg Asp Glu Cys Cys Ser Asn Pro Ala Cys Arg Val
Asn Asn 20 25 30
Pro His Val Cys Arg Arg Arg
35 301151DNAConus
arenatusCDS(1)..(120) 301tct gat ggc agg aat gcc gca gcc aac gcg ttt gac
ctg atg cct ctg 48Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala Phe Asp
Leu Met Pro Leu1 5 10 15
acc gcc agg cta aat tgc tgt agc att ccc ggc tgt tgg aac gaa tat
96Thr Ala Arg Leu Asn Cys Cys Ser Ile Pro Gly Cys Trp Asn Glu Tyr
20 25 30 aaa gac aga tgt agt
aaa gta cgc tgatgctcca ggaccctctg aaccacgacg 150Lys Asp Arg Cys Ser
Lys Val Arg 35
40 t
15130240PRTConus arenatus 302Ser Asp Gly
Arg Asn Ala Ala Ala Asn Ala Phe Asp Leu Met Pro Leu 1 5
10 15 Thr Ala Arg Leu Asn Cys Cys
Ser Ile Pro Gly Cys Trp Asn Glu Tyr 20 25
30 Lys Asp Arg Cys Ser Lys Val Arg
35 40
303157DNAConus aurisiacusCDS(52)..(126) 303tctgatggca ggaatgccgc
agccgacgac aaagcgtctg acctggtcgc t ctg gtc 57
Leu Val
1 gtc agg gga gga tgc tgt tcc cac cct gtc tgt
tac ttt aat aat cca 105Val Arg Gly Gly Cys Cys Ser His Pro Val Cys
Tyr Phe Asn Asn Pro5 10 15
caa atg tgt cgt gga aga cgc tgatgctcca ggaccctctg aaccacgacg t
157Gln Met Cys Arg Gly Arg Arg 20
25 30425PRTConus aurisiacus
304Leu Val Val Arg Gly Gly Cys Cys Ser His Pro Val Cys Tyr Phe Asn 1
5 10 15 Asn Pro Gln Met
Cys Arg Gly Arg Arg 20
25 305157DNAConus
aurisiacusCDS(52)..(126) 305tctgatggca ggaatgccgc agccgacgac aaagcgtctg
acctggtcgc t ctg gcc 57
Leu Ala
1 gtc agg gga gga tgc tgt tcc cac cct gtc tgt aac ttg aat aat cca
105Val Arg Gly Gly Cys Cys Ser His Pro Val Cys Asn Leu Asn Asn Pro5
10 15 caa atg tgt cgt gga aga
cgc tgatgctcca ggaccctctg aaccacgacg t 157Gln Met Cys Arg Gly Arg
Arg 20 25
30625PRTConus aurisiacus 306Leu Ala Val Arg Gly Gly
Cys Cys Ser His Pro Val Cys Asn Leu Asn 1 5
10 15 Asn Pro Gln Met Cys Arg Gly Arg Arg
20 25
307157DNAConus betulinusCDS(1)..(117) 307ttt cgt ggc agg aat
ccc gca gcc aac gac aaa agg tct gac ctg gcc 48Phe Arg Gly Arg Asn
Pro Ala Ala Asn Asp Lys Arg Ser Asp Leu Ala1 5
10 15 gct ctg agc gtc agg gga gga tgc tgt tcc
cat cct gcc tgt agc gtg 96Ala Leu Ser Val Arg Gly Gly Cys Cys Ser
His Pro Ala Cys Ser Val 20 25
30 act cat cca gag ctt tgt ggc tgaagacgct gatgccccag gaccctctga
147Thr His Pro Glu Leu Cys Gly
35 accacgacgt
15730839PRTConus
betulinus 308Phe Arg Gly Arg Asn Pro Ala Ala Asn Asp Lys Arg Ser Asp Leu
Ala 1 5 10 15 Ala
Leu Ser Val Arg Gly Gly Cys Cys Ser His Pro Ala Cys Ser Val
20 25 30 Thr His Pro Glu Leu
Cys Gly 35
309151DNAConus betulinusCDS(1)..(120)
309tct gat ggc ggg aat gcc gca gcc aaa gcg tct gac ctg atc gct cag
48Ser Asp Gly Gly Asn Ala Ala Ala Lys Ala Ser Asp Leu Ile Ala Gln1
5 10 15 acc atc agg gga gga
tgc tgt tcc tat cct gcc tgt agc gtg gaa cat 96Thr Ile Arg Gly Gly
Cys Cys Ser Tyr Pro Ala Cys Ser Val Glu His 20
25 30 caa gac ctt tgt gat gga aga cgc tgatgctcca
ggaccctctg aaccacgacg 150Gln Asp Leu Cys Asp Gly Arg Arg
35 40
t
15131040PRTConus betulinus 310Ser Asp Gly Gly Asn Ala Ala Ala Lys Ala
Ser Asp Leu Ile Ala Gln 1 5 10
15 Thr Ile Arg Gly Gly Cys Cys Ser Tyr Pro Ala Cys Ser Val
Glu His 20 25 30
Gln Asp Leu Cys Asp Gly Arg Arg
35 40 311114DNAConus
caracteristicusCDS(1)..(111) 311tct tat ggc agg aat gcc gca gcc aaa gcg
ttt gaa gtg agt tgc tgt 48Ser Tyr Gly Arg Asn Ala Ala Ala Lys Ala
Phe Glu Val Ser Cys Cys1 5 10
15 gtc gtt cgc ccc tgt tgg att cgc tat caa gag gaa tgt ctt gaa
gca 96Val Val Arg Pro Cys Trp Ile Arg Tyr Gln Glu Glu Cys Leu Glu
Ala 20 25 30 gat ccc
agg acc ctc tga 114Asp Pro
Arg Thr Leu 35 31237PRTConus caracteristicus 312Ser
Tyr Gly Arg Asn Ala Ala Ala Lys Ala Phe Glu Val Ser Cys Cys 1
5 10 15 Val Val Arg Pro Cys
Trp Ile Arg Tyr Gln Glu Glu Cys Leu Glu Ala 20
25 30 Asp Pro Arg Thr Leu
35
313123DNAConus caracteristicusCDS(1)..(120) 313tct gat
ggc agg aat gcc gca gcc aac gcc ctt gac ctg atc act ctg 48Ser Asp
Gly Arg Asn Ala Ala Ala Asn Ala Leu Asp Leu Ile Thr Leu1 5
10 15 atc gcc agg caa aat tgc tgt
agc att ccc ggc tgt tgg gag aaa tat 96Ile Ala Arg Gln Asn Cys Cys
Ser Ile Pro Gly Cys Trp Glu Lys Tyr 20 25
30 gga gac aaa tgt agt gaa gta cgc tga
123Gly Asp Lys Cys Ser Glu Val Arg 35
40 31440PRTConus caracteristicus 314Ser Asp Gly Arg Asn Ala
Ala Ala Asn Ala Leu Asp Leu Ile Thr Leu 1 5
10 15 Ile Ala Arg Gln Asn Cys Cys Ser Ile Pro
Gly Cys Trp Glu Lys Tyr 20 25
30 Gly Asp Lys Cys Ser Glu Val Arg
35 40
315154DNAConus catusCDS(1)..(123) 315tct gat ggc agg aat gaa gca gcc aac
gac gaa gcg tct gac gtg atc 48Ser Asp Gly Arg Asn Glu Ala Ala Asn
Asp Glu Ala Ser Asp Val Ile1 5 10
15 gag ctg gcc ctc aag gga tgc tgt tcc aac cct gtc tgt cac
ttg gag 96Glu Leu Ala Leu Lys Gly Cys Cys Ser Asn Pro Val Cys His
Leu Glu 20 25 30 cat
cca aac gct tgt ggt aga aga cgc tgatgctcca ggaccctctg 143His
Pro Asn Ala Cys Gly Arg Arg Arg 35
40 aaccacgacg t
15431641PRTConus catus 316Ser Asp Gly Arg
Asn Glu Ala Ala Asn Asp Glu Ala Ser Asp Val Ile 1 5
10 15 Glu Leu Ala Leu Lys Gly Cys Cys
Ser Asn Pro Val Cys His Leu Glu 20 25
30 His Pro Asn Ala Cys Gly Arg Arg Arg
35 40
317154DNAConus catusCDS(1)..(123) 317tct gat ggc agg aat gcc gca gcc
aac gac aaa gcg tct gac ctg gtc 48Ser Asp Gly Arg Asn Ala Ala Ala
Asn Asp Lys Ala Ser Asp Leu Val1 5 10
15 gct ctg gcc gtc agg gga tgc tgt tcc aac cct atc tgt
tac ttt aat 96Ala Leu Ala Val Arg Gly Cys Cys Ser Asn Pro Ile Cys
Tyr Phe Asn 20 25 30
aat cca cga att tgt cgt gga aga cgc tgatgctcca ggaccctctg
143Asn Pro Arg Ile Cys Arg Gly Arg Arg 35
40 aaccacgacg t
15431841PRTConus catus 318Ser Asp
Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Asp Leu Val 1
5 10 15 Ala Leu Ala Val Arg Gly
Cys Cys Ser Asn Pro Ile Cys Tyr Phe Asn 20
25 30 Asn Pro Arg Ile Cys Arg Gly Arg Arg
35 40
319111DNAConus episcopatusCDS(1)..(108) 319tct cat ggc agg
aat gcc gca cgc aaa gcg tct gac ctg atc gct ctg 48Ser His Gly Arg
Asn Ala Ala Arg Lys Ala Ser Asp Leu Ile Ala Leu1 5
10 15 acc gtc agg gaa tgc tgt tct cag cct
ccc tgt cgc tgg aaa cat cca 96Thr Val Arg Glu Cys Cys Ser Gln Pro
Pro Cys Arg Trp Lys His Pro 20 25
30 gaa ctt tgt agt tga
111Glu Leu Cys Ser 35 32036PRTConus
episcopatus 320Ser His Gly Arg Asn Ala Ala Arg Lys Ala Ser Asp Leu Ile
Ala Leu 1 5 10 15
Thr Val Arg Glu Cys Cys Ser Gln Pro Pro Cys Arg Trp Lys His Pro
20 25 30 Glu Leu Cys Ser
35
321151DNAConus
geographusCDS(1)..(120) 321tct gat ggc agg aat gac gca gcc aaa gcg ttt
gac ctg ata tct tcg 48Ser Asp Gly Arg Asn Asp Ala Ala Lys Ala Phe
Asp Leu Ile Ser Ser1 5 10
15 acc gtc aag aaa gga tgc tgt tcc cat cct gcc tgt gcg ggg aat aat
96Thr Val Lys Lys Gly Cys Cys Ser His Pro Ala Cys Ala Gly Asn Asn
20 25 30 caa cat att tgt
ggc cga aga cgc tgatgctcca ggaccctctg aaccacgacg 150Gln His Ile Cys
Gly Arg Arg Arg 35
40 t
15132240PRTConus geographus 322Ser Asp
Gly Arg Asn Asp Ala Ala Lys Ala Phe Asp Leu Ile Ser Ser 1
5 10 15 Thr Val Lys Lys Gly Cys
Cys Ser His Pro Ala Cys Ala Gly Asn Asn 20
25 30 Gln His Ile Cys Gly Arg Arg Arg
35 40
323154DNAConus geographusCDS(1)..(123) 323tct gat ggc agg
aat gcc gca gcc aac gac caa gcg tct gac ctg atg 48Ser Asp Gly Arg
Asn Ala Ala Ala Asn Asp Gln Ala Ser Asp Leu Met1 5
10 15 gct gcg acc gtc agg gga tgc tgt gcc
gtt cct tcc tgt cgc ctc cgt 96Ala Ala Thr Val Arg Gly Cys Cys Ala
Val Pro Ser Cys Arg Leu Arg 20 25
30 aat cca gac ctt tgt ggt gga gga cgc tgatgctcca ggaccctctg
143Asn Pro Asp Leu Cys Gly Gly Gly Arg
35 40 aaccacgacg t
15432441PRTConus
geographus 324Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Gln Ala Ser Asp Leu
Met 1 5 10 15 Ala
Ala Thr Val Arg Gly Cys Cys Ala Val Pro Ser Cys Arg Leu Arg
20 25 30 Asn Pro Asp Leu Cys
Gly Gly Gly Arg 35
40 325120DNAConus
imperialisCDS(1)..(117) 325ctt gat gaa agg aat gcc gca gcc gac gac aaa
gcg tct gac ctg atc 48Leu Asp Glu Arg Asn Ala Ala Ala Asp Asp Lys
Ala Ser Asp Leu Ile1 5 10
15 gct caa atc gtc agg aga gga tgc tgt tcc cat cct gcc tgt aac gtg
96Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Ala Cys Asn Val
20 25 30 aat aat cca cac
att tgt ggt tga 120Asn Asn Pro His
Ile Cys Gly 35 32639PRTConus imperialis
326Leu Asp Glu Arg Asn Ala Ala Ala Asp Asp Lys Ala Ser Asp Leu Ile 1
5 10 15 Ala Gln Ile Val
Arg Arg Gly Cys Cys Ser His Pro Ala Cys Asn Val 20
25 30 Asn Asn Pro His Ile Cys Gly
35
327142DNAConus lividusCDS(1)..(111) 327tct gat ggc
agg aat act gca gcc aaa gtc aaa tat tct aag acg ccg 48Ser Asp Gly
Arg Asn Thr Ala Ala Lys Val Lys Tyr Ser Lys Thr Pro1 5
10 15 gag gaa tgc tgt ccc aat cct ccc
tgt ttc gcg aca aat tcg gat att 96Glu Glu Cys Cys Pro Asn Pro Pro
Cys Phe Ala Thr Asn Ser Asp Ile 20 25
30 tgt ggc gga aga cgc tgatgctcca ggaccctctg aaccacgacg t
142Cys Gly Gly Arg Arg
35 32837PRTConus lividus
328Ser Asp Gly Arg Asn Thr Ala Ala Lys Val Lys Tyr Ser Lys Thr Pro 1
5 10 15 Glu Glu Cys Cys
Pro Asn Pro Pro Cys Phe Ala Thr Asn Ser Asp Ile 20
25 30 Cys Gly Gly Arg Arg
35
329157DNAConus lividusCDS(1)..(117) 329tct aat ggc
agg aat gcc gca gcc aaa ttc aaa gcg cct gcc ctg atg 48Ser Asn Gly
Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met1 5
10 15 aag cgg acc gtc agg gat gct tgc
tgt tca gac cct cgc tgt tcc ggg 96Lys Arg Thr Val Arg Asp Ala Cys
Cys Ser Asp Pro Arg Cys Ser Gly 20 25
30 aaa cat caa gac ctg tgt ggc tgaagacgct gatgctccag
gaccctctga 147Lys His Gln Asp Leu Cys Gly
35
accacgacgt
15733039PRTConus lividus 330Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys
Ala Pro Ala Leu Met 1 5 10
15 Lys Arg Thr Val Arg Asp Ala Cys Cys Ser Asp Pro Arg Cys Ser
Gly 20 25 30 Lys
His Gln Asp Leu Cys Gly 35
331157DNAConus
lividusCDS(1)..(117) 331tct aat ggc agg aat gcc gca gcc aaa ttc aaa gcg
cct gcc ctg atg 48Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala
Pro Ala Leu Met1 5 10 15
gag ctg acc gtc agg gaa gat tgc tgt tca gac cct cgc tgt tcc gtg
96Glu Leu Thr Val Arg Glu Asp Cys Cys Ser Asp Pro Arg Cys Ser Val
20 25 30 gga cat caa gac ctg
tgt ggc tgaagacgct gatgctccag gaccctctga 147Gly His Gln Asp Leu
Cys Gly 35
accacgacgt
15733239PRTConus lividus 332Ser Asn Gly Arg Asn Ala
Ala Ala Lys Phe Lys Ala Pro Ala Leu Met 1 5
10 15 Glu Leu Thr Val Arg Glu Asp Cys Cys Ser
Asp Pro Arg Cys Ser Val 20 25
30 Gly His Gln Asp Leu Cys Gly
35
333157DNAConus lividusCDS(1)..(126) 333gca ttt gat ggc agg aat gct gca
gcc agc gac aaa gcg tcc gag ctg 48Ala Phe Asp Gly Arg Asn Ala Ala
Ala Ser Asp Lys Ala Ser Glu Leu1 5 10
15 atg gct ctg gcc gtc agg gga tgc tgt tcc cat cct gcc
tgt gct ggg 96Met Ala Leu Ala Val Arg Gly Cys Cys Ser His Pro Ala
Cys Ala Gly 20 25 30
agt aat gca cat atc tgt ggc aga aga cgc tgatgctcca ggaccctctg
146Ser Asn Ala His Ile Cys Gly Arg Arg Arg
35 40 aaccacgacg t
15733442PRTConus lividus
334Ala Phe Asp Gly Arg Asn Ala Ala Ala Ser Asp Lys Ala Ser Glu Leu 1
5 10 15 Met Ala Leu Ala
Val Arg Gly Cys Cys Ser His Pro Ala Cys Ala Gly 20
25 30 Ser Asn Ala His Ile Cys Gly Arg
Arg Arg 35 40
335157DNAConus lividusCDS(1)..(117) 335tct aat ggc
agg aat gcc gca gcc aaa ttc aaa gcg cct gcc ctg atg 48Ser Asn Gly
Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met1 5
10 15 aag ctg acc gtc agg gag gat tgc
tgt tca gac cct cgc tgt tcc gtg 96Lys Leu Thr Val Arg Glu Asp Cys
Cys Ser Asp Pro Arg Cys Ser Val 20 25
30 gga cat caa gac atg tgt ggc tgaagacgct gatgctccag
gaccctctga 147Gly His Gln Asp Met Cys Gly
35
atcacgacgt
15733639PRTConus lividus 336Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys
Ala Pro Ala Leu Met 1 5 10
15 Lys Leu Thr Val Arg Glu Asp Cys Cys Ser Asp Pro Arg Cys Ser
Val 20 25 30 Gly
His Gln Asp Met Cys Gly 35
337154DNAConus
lividusCDS(1)..(114) 337ttt gaa tgc agg aat gct gca ggc aac gac aaa gcg
act gac ctg atg 48Phe Glu Cys Arg Asn Ala Ala Gly Asn Asp Lys Ala
Thr Asp Leu Met1 5 10 15
gct ctg act gtc agg gga tgc tgt tcc cat cct gcc tgt gct ggg aat
96Ala Leu Thr Val Arg Gly Cys Cys Ser His Pro Ala Cys Ala Gly Asn
20 25 30 aat cca cat atc tgc
ggc tgaagacgct gatgctccag gaccctctga 144Asn Pro His Ile Cys
Gly 35
accacgacgt
15433838PRTConus lividus 338Phe Glu Cys Arg Asn Ala Ala Gly
Asn Asp Lys Ala Thr Asp Leu Met 1 5 10
15 Ala Leu Thr Val Arg Gly Cys Cys Ser His Pro Ala
Cys Ala Gly Asn 20 25 30
Asn Pro His Ile Cys Gly
35
339154DNAConus lividusCDS(1)..(114) 339ttt gat ggc agg aac gcc gca gcc
aac aac aaa gcg act gat ctg atg 48Phe Asp Gly Arg Asn Ala Ala Ala
Asn Asn Lys Ala Thr Asp Leu Met1 5 10
15 gct ctg act gtc aga gga tgc tgt ggc aat cct tca tgt
agc atc cat 96Ala Leu Thr Val Arg Gly Cys Cys Gly Asn Pro Ser Cys
Ser Ile His 20 25 30
att cct tac gtt tgt aat tagagacact gatgctccag gaccctctga
144Ile Pro Tyr Val Cys Asn 35
accacgacgt
15434038PRTConus lividus 340Phe Asp
Gly Arg Asn Ala Ala Ala Asn Asn Lys Ala Thr Asp Leu Met 1
5 10 15 Ala Leu Thr Val Arg Gly
Cys Cys Gly Asn Pro Ser Cys Ser Ile His 20
25 30 Ile Pro Tyr Val Cys Asn
35
341157DNAConus lividusCDS(1)..(126) 341tct aat ggc agg aat
gcc gca gcc aaa ttc aaa gcg cct gcc ctg atg 48Ser Asn Gly Arg Asn
Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met1 5
10 15 aag cgg acc gac agc gaa gaa tgc tgt tta
gac tct cgc tgt gcc ggg 96Lys Arg Thr Asp Ser Glu Glu Cys Cys Leu
Asp Ser Arg Cys Ala Gly 20 25
30 caa cat caa gac ctg tgt ggc gga aga cgc tgatgctcca ggaccctctg
146Gln His Gln Asp Leu Cys Gly Gly Arg Arg
35 40 aaccacgacg t
15734242PRTConus
lividus 342Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu
Met 1 5 10 15 Lys
Arg Thr Asp Ser Glu Glu Cys Cys Leu Asp Ser Arg Cys Ala Gly
20 25 30 Gln His Gln Asp Leu
Cys Gly Gly Arg Arg 35
40 343126DNAConus marmoreusCDS(1)..(123)
343tct gat ggc agg aat gcc gca gcc aag gac aaa gcg tct gac ctg gtc
48Ser Asp Gly Arg Asn Ala Ala Ala Lys Asp Lys Ala Ser Asp Leu Val1
5 10 15 gct ctg acc gtc aag
gga tgc tgt tct aat cct ccc tgt tac gcg aat 96Ala Leu Thr Val Lys
Gly Cys Cys Ser Asn Pro Pro Cys Tyr Ala Asn 20
25 30 aat caa gcc tat tgt aat gga aga cgc tga
126Asn Gln Ala Tyr Cys Asn Gly Arg Arg
35 40 34441PRTConus marmoreus 344Ser Asp Gly
Arg Asn Ala Ala Ala Lys Asp Lys Ala Ser Asp Leu Val 1 5
10 15 Ala Leu Thr Val Lys Gly Cys
Cys Ser Asn Pro Pro Cys Tyr Ala Asn 20 25
30 Asn Gln Ala Tyr Cys Asn Gly Arg Arg
35 40
345117DNAConus marmoreusCDS(1)..(114) 345tct gat ggc agg aat gcc
gca gcc aag gac aaa gcg tct gac ctg gtc 48Ser Asp Gly Arg Asn Ala
Ala Ala Lys Asp Lys Ala Ser Asp Leu Val1 5
10 15 gct ctg acc gtc aag gga tgc tgt tct cat cct
gcc tgt agc gtg aat 96Ala Leu Thr Val Lys Gly Cys Cys Ser His Pro
Ala Cys Ser Val Asn 20 25 30
aat cca gac att tgt ggt tga
117Asn Pro Asp Ile Cys Gly 35 34638PRTConus
marmoreus 346Ser Asp Gly Arg Asn Ala Ala Ala Lys Asp Lys Ala Ser Asp Leu
Val 1 5 10 15 Ala
Leu Thr Val Lys Gly Cys Cys Ser His Pro Ala Cys Ser Val Asn
20 25 30 Asn Pro Asp Ile Cys
Gly 35
347145DNAConus musicusCDS(1)..(114)
347tct gat ggc agg aat gct gca gcc aac aac aaa gtg gct ttg acc atg
48Ser Asp Gly Arg Asn Ala Ala Ala Asn Asn Lys Val Ala Leu Thr Met1
5 10 15 agg gga aaa tgc tgt
atc aat gat gcg tgt cgc tcg aaa cat cca cag 96Arg Gly Lys Cys Cys
Ile Asn Asp Ala Cys Arg Ser Lys His Pro Gln 20
25 30 tac tgt tct gga aga cgc tgatactcca
ggaccctctg aaccacgacg t 145Tyr Cys Ser Gly Arg Arg
35
34838PRTConus musicus 348Ser Asp Gly Arg Asn Ala Ala Ala Asn Asn Lys
Val Ala Leu Thr Met 1 5 10
15 Arg Gly Lys Cys Cys Ile Asn Asp Ala Cys Arg Ser Lys His Pro
Gln 20 25 30 Tyr
Cys Ser Gly Arg Arg 35
349154DNAConus
musicusCDS(1)..(123) 349tct gat ggc agg aat gct gca gcc aac gac aaa gtg
tct gac cag atg 48Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Val
Ser Asp Gln Met1 5 10 15
gct ctg gtt gtc agg gga tgc tgt tac aat att gcc tgt aga att aat
96Ala Leu Val Val Arg Gly Cys Cys Tyr Asn Ile Ala Cys Arg Ile Asn
20 25 30 aat cca cgg tac tgt
cgt gga aaa cgc tgatgttcca ggaccctctg 143Asn Pro Arg Tyr Cys
Arg Gly Lys Arg 35 40
aaccacgacg t
15435041PRTConus musicus 350Ser Asp Gly Arg Asn Ala Ala Ala
Asn Asp Lys Val Ser Asp Gln Met 1 5 10
15 Ala Leu Val Val Arg Gly Cys Cys Tyr Asn Ile Ala
Cys Arg Ile Asn 20 25 30
Asn Pro Arg Tyr Cys Arg Gly Lys Arg
35 40
351154DNAConus obscurusCDS(52)..(123) 351tctgaaggca ggaatgccgc agccaacgac
aaagcgtctg acctgatggc t ctg aac 57
Leu Asn
1 gtc agg gga tgc tgt tcc cat cct gtc tgt cgc ttc aat
tat cca aaa 105Val Arg Gly Cys Cys Ser His Pro Val Cys Arg Phe Asn
Tyr Pro Lys5 10 15 tat tgt
ggt gga aga cgc tgatggtcca ggaccctctg aaccacgacg t 154Tyr Cys
Gly Gly Arg Arg 20
35224PRTConus obscurus 352Leu Asn Val Arg
Gly Cys Cys Ser His Pro Val Cys Arg Phe Asn Tyr 1 5
10 15 Pro Lys Tyr Cys Gly Gly Arg Arg
20
353151DNAConus obscurusCDS(46)..(111) 353tctgatggcg
ggaatgccgc agcaaaagcg tttgatctaa tcact ctg gcc ctc agg 57
Leu Ala Leu Arg
1 gat gaa tgc tgt gcc agt cct
ccc tgt cgt ttg aat aat cca tac gta 105Asp Glu Cys Cys Ala Ser Pro
Pro Cys Arg Leu Asn Asn Pro Tyr Val5 10
15 20tgt cat tgacgacgct gatgctccag gaccctctga
accacgacgt 151Cys His
35422PRTConus obscurus 354Leu Ala Leu Arg Asp Glu Cys Cys Ala Ser
Pro Pro Cys Arg Leu Asn 1 5 10
15 Asn Pro Tyr Val Cys His
20
355217DNAConus obscurusCDS(1)..(186) 355atg ttc acc gtg ttt ctg ttg gtt
gtc ttg gca acc acc gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val
Val Leu Ala Thr Thr Val Val Ser1 5 10
15 ccc act tca gat cgt gca tct gat agg agg aat gcc gca
gcc aaa gcg 96Pro Thr Ser Asp Arg Ala Ser Asp Arg Arg Asn Ala Ala
Ala Lys Ala 20 25 30
ttt gac ctg aga tat tcg acc gcc aag aga gga tgc tgt tcc aat cct
144Phe Asp Leu Arg Tyr Ser Thr Ala Lys Arg Gly Cys Cys Ser Asn Pro
35 40 45 gtc tgt tgg cag aat
aat gca gaa tac tgt cgt gaa agt ggc 186Val Cys Trp Gln Asn
Asn Ala Glu Tyr Cys Arg Glu Ser Gly 50 55
60 taatgctcca ggaccctctg aaccacgacg t
21735662PRTConus obscurus 356Met Phe Thr Val Phe Leu Leu Val
Val Leu Ala Thr Thr Val Val Ser 1 5 10
15 Pro Thr Ser Asp Arg Ala Ser Asp Arg Arg Asn Ala
Ala Ala Lys Ala 20 25 30
Phe Asp Leu Arg Tyr Ser Thr Ala Lys Arg Gly Cys Cys Ser Asn Pro
35 40 45 Val Cys Trp
Gln Asn Asn Ala Glu Tyr Cys Arg Glu Ser Gly 50
55 60 357208DNAConus
obscurusCDS(1)..(168) 357atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc
acc gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr
Thr Val Val Ser1 5 10 15
ttc act tca gat cgt gca tct gat ggc ggg aat gtc gca gcg tct cac
96Phe Thr Ser Asp Arg Ala Ser Asp Gly Gly Asn Val Ala Ala Ser His
20 25 30 ctg atc gct ctg acc
atc aag gga tgc tgt tct cac cct ccc tgt gcc 144Leu Ile Ala Leu Thr
Ile Lys Gly Cys Cys Ser His Pro Pro Cys Ala 35 40
45 cag aat aat caa gac tat tgt ggt tgacgacgct
gatgctccag gaccctctga 198Gln Asn Asn Gln Asp Tyr Cys Gly
50 55
accacgacgt
20835856PRTConus obscurus 358Met Phe Thr Val Phe Leu Leu Val Val Leu
Ala Thr Thr Val Val Ser 1 5 10
15 Phe Thr Ser Asp Arg Ala Ser Asp Gly Gly Asn Val Ala Ala
Ser His 20 25 30
Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser His Pro Pro Cys Ala
35 40 45 Gln Asn Asn Gln
Asp Tyr Cys Gly 50
55 359217DNAConus
obscurusCDS(1)..(186) 359atg ttc acc gtg ttt ctg ttg gtt gtc tta tca acc
acc gtc gtt tcc 48Met Phe Thr Val Phe Leu Leu Val Val Leu Ser Thr
Thr Val Val Ser1 5 10 15
tcc act tca gat cgt gca tct gat agg agg aat gcc gca gcc aaa gcg
96Ser Thr Ser Asp Arg Ala Ser Asp Arg Arg Asn Ala Ala Ala Lys Ala
20 25 30 tct gac ctg atg tat
tcg acc gtc aag aaa gga tgt tgt tcc cat cct 144Ser Asp Leu Met Tyr
Ser Thr Val Lys Lys Gly Cys Cys Ser His Pro 35 40
45 gcc tgt tcg ggg aat aat cga gaa tat tgt
cgt gaa agt ggc 186Ala Cys Ser Gly Asn Asn Arg Glu Tyr Cys
Arg Glu Ser Gly 50 55 60
taatgctcca ggaccctctg aaccacgacg t
21736062PRTConus obscurus 360Met Phe Thr Val Phe Leu Leu Val Val Leu Ser
Thr Thr Val Val Ser 1 5 10
15 Ser Thr Ser Asp Arg Ala Ser Asp Arg Arg Asn Ala Ala Ala Lys
Ala 20 25 30 Ser
Asp Leu Met Tyr Ser Thr Val Lys Lys Gly Cys Cys Ser His Pro 35
40 45 Ala Cys Ser Gly Asn
Asn Arg Glu Tyr Cys Arg Glu Ser Gly 50 55
60 361157DNAConus omariaCDS(52)..(126)
361tttgatggca ggaatgcctc agccgacagc aaagtggctg cccggatcgc t cag atc
57 Gln Ile
1 gac agg gat cca
tgc tgt tcc tat cct gac tgt ggc gcg aat cat cca 105Asp Arg Asp Pro
Cys Cys Ser Tyr Pro Asp Cys Gly Ala Asn His Pro5 10
15 gag att tgt ggt gga aaa cgc tgatgctcca
ggaccctctg aaccacgacg t 157Glu Ile Cys Gly Gly Lys Arg
20 25
36225PRTConus omaria 362Gln Ile Asp Arg Asp Pro Cys Cys Ser Tyr Pro
Asp Cys Gly Ala Asn 1 5 10
15 His Pro Glu Ile Cys Gly Gly Lys Arg
20 25
363128DNAConus omariaCDS(26)..(88) 363tctcatggca ggaatgccgc acgct ctg acc
gtc agg gaa tgc tgt tct cag 52 Leu Thr
Val Arg Glu Cys Cys Ser Gln 1
5 cct cct tgt cgc tgg aaa cat cca gaa ctt tgt agt
tgaagacgct 98Pro Pro Cys Arg Trp Lys His Pro Glu Leu Cys Ser
10 15 20
gatgctccag gaccctctga accacgacgt
12836421PRTConus omaria 364Leu Thr Val Arg Glu Cys Cys Ser Gln Pro Pro
Cys Arg Trp Lys His 1 5 10
15 Pro Glu Leu Cys Ser
20
365154DNAConus omariaCDS(52)..(123) 365tttgatggca ggaatgctgc agccagcgac
aaagcgtctg agctgatggc t ctg gcc 57
Leu Ala
1 gtc agg gga tgc tgt tcc cat cct gcc tgt gct ggg aat
aat cca cat 105Val Arg Gly Cys Cys Ser His Pro Ala Cys Ala Gly Asn
Asn Pro His5 10 15 atc tgt
ggc aga aga cgc tgatgctcca ggaccctctg aaccacgacg t 154Ile Cys
Gly Arg Arg Arg 20
36624PRTConus omaria 366Leu Ala Val Arg Gly
Cys Cys Ser His Pro Ala Cys Ala Gly Asn Asn 1 5
10 15 Pro His Ile Cys Gly Arg Arg Arg
20
367142DNAConus omariaCDS(40)..(102) 367tctggtgtca
ggaaagacgc agcgcctggc ctgatcgct ctg acc atc aag gga 54
Leu Thr Ile Lys Gly
1 5tgc tgt tct gat cct agc tgt aac gtg
aat aat cca gac tat tgt ggt 102Cys Cys Ser Asp Pro Ser Cys Asn Val
Asn Asn Pro Asp Tyr Cys Gly 10 15
20 tgacgacgct gatgctccag gaccctctga accacgacgt
14236821PRTConus omaria 368Leu Thr Ile Lys Gly Cys Cys Ser Asp
Pro Ser Cys Asn Val Asn Asn 1 5 10
15 Pro Asp Tyr Cys Gly
20
369157DNAConus omariaCDS(52)..(117) 369tctaatggca ggaatgccgc agccaaattc
aaagcgcctg ccctgatgga g ctg acc 57
Leu Thr
1 gtc agg gaa gaa tgc tgt tca gac cct cgc tgt tcc gtg
gga cat caa 105Val Arg Glu Glu Cys Cys Ser Asp Pro Arg Cys Ser Val
Gly His Gln5 10 15 gat atg
tgt cgg tgaagcacgt gatgctccag gaccctctga accacgacgt 157Asp Met
Cys Arg 20
37022PRTConus omaria 370Leu Thr Val Arg
Glu Glu Cys Cys Ser Asp Pro Arg Cys Ser Val Gly 1 5
10 15 His Gln Asp Met Cys Arg
20
371151DNAConus purpurascensCDS(1)..(120) 371act gat
ggc agg aat gct gca gcc ata gcg ctt gac ctg atc gct ccg 48Thr Asp
Gly Arg Asn Ala Ala Ala Ile Ala Leu Asp Leu Ile Ala Pro1 5
10 15 gcc gtc agg gga gga tgc tgt
tcc aat cct gcc tgt tta gtg aat cat 96Ala Val Arg Gly Gly Cys Cys
Ser Asn Pro Ala Cys Leu Val Asn His 20 25
30 cta gaa atg tgt ggt aaa aga cgc tgatgcccca
ggaccctctg aaccacgacg 150Leu Glu Met Cys Gly Lys Arg Arg
35 40
t
15137240PRTConus purpurascens 372Thr Asp Gly Arg Asn Ala Ala Ala Ile
Ala Leu Asp Leu Ile Ala Pro 1 5 10
15 Ala Val Arg Gly Gly Cys Cys Ser Asn Pro Ala Cys Leu
Val Asn His 20 25 30
Leu Glu Met Cys Gly Lys Arg Arg
35 40 373160DNAConus
purpurascensCDS(1)..(120) 373tct gat ggc agg gat gcc gca gcc aac gac aaa
gcg tct gac ctg atc 48Ser Asp Gly Arg Asp Ala Ala Ala Asn Asp Lys
Ala Ser Asp Leu Ile1 5 10
15 gct ctg acc gcc agg aga gat cca tgc tgt ttc aat cct gcc tgt aac
96Ala Leu Thr Ala Arg Arg Asp Pro Cys Cys Phe Asn Pro Ala Cys Asn
20 25 30 gtg aat aat cca
cag att tgt ggt tgaagacgct gatgctccag gaccctctga 150Val Asn Asn Pro
Gln Ile Cys Gly 35
40 accacgacgt
16037440PRTConus purpurascens 374Ser Asp
Gly Arg Asp Ala Ala Ala Asn Asp Lys Ala Ser Asp Leu Ile 1
5 10 15 Ala Leu Thr Ala Arg Arg
Asp Pro Cys Cys Phe Asn Pro Ala Cys Asn 20
25 30 Val Asn Asn Pro Gln Ile Cys Gly
35 40
375151DNAConus purpurascensCDS(1)..(120) 375tct gat ggc agg
gat gct gag aaa aca ggc ttt gac acg acc att gtg 48Ser Asp Gly Arg
Asp Ala Glu Lys Thr Gly Phe Asp Thr Thr Ile Val1 5
10 15 ccg gaa gac tgc tgt tcg gat cct tcc
tgt tgg agg ctg cat agt tta 96Pro Glu Asp Cys Cys Ser Asp Pro Ser
Cys Trp Arg Leu His Ser Leu 20 25
30 gct tgt act gga att gta aac cgc tgatgctcca ggaccctctg
aaccacgacg 150Ala Cys Thr Gly Ile Val Asn Arg
35 40 t
15137640PRTConus purpurascens 376Ser Asp Gly Arg Asp Ala Glu Lys Thr Gly
Phe Asp Thr Thr Ile Val 1 5 10
15 Pro Glu Asp Cys Cys Ser Asp Pro Ser Cys Trp Arg Leu His
Ser Leu 20 25 30
Ala Cys Thr Gly Ile Val Asn Arg
35 40 377142DNAConus
purpurascensCDS(1)..(111) 377act gat ggc agg agt gct gca gcc ata gcg ttt
gcc ctg atc gct ccg 48Thr Asp Gly Arg Ser Ala Ala Ala Ile Ala Phe
Ala Leu Ile Ala Pro1 5 10
15 acc gtc tgc tgt act aat cct gcc tgt ctc gtg aat aat ata cgc ttt
96Thr Val Cys Cys Thr Asn Pro Ala Cys Leu Val Asn Asn Ile Arg Phe
20 25 30 tgt ggt gga aga
cgc tgatgcccca ggaccctctg aaccacgacg t 142Cys Gly Gly Arg
Arg 35
37837PRTConus purpurascens 378Thr Asp Gly Arg Ser Ala
Ala Ala Ile Ala Phe Ala Leu Ile Ala Pro 1 5
10 15 Thr Val Cys Cys Thr Asn Pro Ala Cys Leu
Val Asn Asn Ile Arg Phe 20 25
30 Cys Gly Gly Arg Arg
35
379157DNAConus regiusCDS(1)..(117) 379tct gat gga aga aat gcc gca agc gac
gcc aaa gcg ttt ccc cgg atc 48Ser Asp Gly Arg Asn Ala Ala Ser Asp
Ala Lys Ala Phe Pro Arg Ile1 5 10
15 gct cca atc gtc agg gac gaa tgc tgt agc gat cct agg tgt
cac ggg 96Ala Pro Ile Val Arg Asp Glu Cys Cys Ser Asp Pro Arg Cys
His Gly 20 25 30 aat
aat cgg gac cac tgt gct tgaagacgct gctgctccag gaccctctga 147Asn
Asn Arg Asp His Cys Ala 35
accacgacgt
15738039PRTConus regius 380Ser Asp
Gly Arg Asn Ala Ala Ser Asp Ala Lys Ala Phe Pro Arg Ile 1
5 10 15 Ala Pro Ile Val Arg Asp
Glu Cys Cys Ser Asp Pro Arg Cys His Gly 20
25 30 Asn Asn Arg Asp His Cys Ala
35
381156DNAConus regiusCDS(1)..(117) 381tct gat ggc agg aat
acc gcg gcc gac gaa aaa gcg tcc gac ctg atc 48Ser Asp Gly Arg Asn
Thr Ala Ala Asp Glu Lys Ala Ser Asp Leu Ile1 5
10 15 tct caa act gtc aag aga gat tgc tgt tcc
cat cct ctc tgt aga tta 96Ser Gln Thr Val Lys Arg Asp Cys Cys Ser
His Pro Leu Cys Arg Leu 20 25
30 ttt gtt cca gga ctt tgt att tgaagacgct gctgctccag gaccctctga
147Phe Val Pro Gly Leu Cys Ile
35 accacgact
15638239PRTConus regius
382Ser Asp Gly Arg Asn Thr Ala Ala Asp Glu Lys Ala Ser Asp Leu Ile 1
5 10 15 Ser Gln Thr Val
Lys Arg Asp Cys Cys Ser His Pro Leu Cys Arg Leu 20
25 30 Phe Val Pro Gly Leu Cys Ile
35
383157DNAConus regiusCDS(1)..(117) 383tct gat ggc agg
aat gcc gca gcc gac aac aaa gcg tct gac cta atc 48Ser Asp Gly Arg
Asn Ala Ala Ala Asp Asn Lys Ala Ser Asp Leu Ile1 5
10 15 gct caa atc gtc agg aga gga tgc tgt
tcc cat cct gtc tgt aaa gtg 96Ala Gln Ile Val Arg Arg Gly Cys Cys
Ser His Pro Val Cys Lys Val 20 25
30 agg tat cca gac ctg tgt cgt tgaagacgct gctgctccag
gaccctctga 147Arg Tyr Pro Asp Leu Cys Arg
35
accacgacgt
15738439PRTConus regius 384Ser Asp Gly Arg Asn Ala Ala Ala Asp Asn Lys
Ala Ser Asp Leu Ile 1 5 10
15 Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Val Cys Lys
Val 20 25 30 Arg
Tyr Pro Asp Leu Cys Arg 35
385157DNAConus
regiusCDS(1)..(117) 385tct gat ggc agg aat gcc gca gcc gac aac aga gcg
tct gac cta atc 48Ser Asp Gly Arg Asn Ala Ala Ala Asp Asn Arg Ala
Ser Asp Leu Ile1 5 10 15
gct caa atc gtc agg aga gga tgc tgt tcc cat cct gcc tgt aat gtg
96Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Ala Cys Asn Val
20 25 30 aat aat cca cac att
tgt ggt tgaagacgct gctgctccag gaccctctga 147Asn Asn Pro His Ile
Cys Gly 35
accacgacgt
15738639PRTConus regius 386Ser Asp Gly Arg Asn Ala
Ala Ala Asp Asn Arg Ala Ser Asp Leu Ile 1 5
10 15 Ala Gln Ile Val Arg Arg Gly Cys Cys Ser
His Pro Ala Cys Asn Val 20 25
30 Asn Asn Pro His Ile Cys Gly
35
387157DNAConus regiusCDS(1)..(117) 387tct gat ggc agg aat gcc gca gcc gac
aac aaa ccg tct gac cta atc 48Ser Asp Gly Arg Asn Ala Ala Ala Asp
Asn Lys Pro Ser Asp Leu Ile1 5 10
15 gct caa atc gtc agg aga gga tgc tgt tcg cat cct gtc tgt
aaa gtg 96Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Val Cys
Lys Val 20 25 30 agg
tat tca gac atg tgt ggt tgaagacgct gctgctccag gaccctctga 147Arg
Tyr Ser Asp Met Cys Gly 35
accacgacgt
15738839PRTConus regius 388Ser Asp
Gly Arg Asn Ala Ala Ala Asp Asn Lys Pro Ser Asp Leu Ile 1
5 10 15 Ala Gln Ile Val Arg Arg
Gly Cys Cys Ser His Pro Val Cys Lys Val 20
25 30 Arg Tyr Ser Asp Met Cys Gly
35
389154DNAConus stercusmuscarumCDS(1)..(114) 389tct gat ggc
agg aat gca gag cga cga caa agc gtc tgt cct ggt cgc 48Ser Asp Gly
Arg Asn Ala Glu Arg Arg Gln Ser Val Cys Pro Gly Arg1 5
10 15 tct ggc ccc agg gga gga tgt tgt
tcc cac cct gcc tgt aag gtg cat 96Ser Gly Pro Arg Gly Gly Cys Cys
Ser His Pro Ala Cys Lys Val His 20 25
30 ttt cca cac agt tgt ggt tgacgacgct gatgctccag
gaccctctga 144Phe Pro His Ser Cys Gly
35 accacgacgt
15439038PRTConus stercusmuscarum 390Ser Asp Gly Arg Asn Ala Glu Arg Arg
Gln Ser Val Cys Pro Gly Arg 1 5 10
15 Ser Gly Pro Arg Gly Gly Cys Cys Ser His Pro Ala Cys
Lys Val His 20 25 30
Phe Pro His Ser Cys Gly
35 391145DNAConus
stercusmuscarumCDS(1)..(114) 391tct gat ggc agg aat gcc gca gcc agc gac
aga gcg tct gac gcg gcc 48Ser Asp Gly Arg Asn Ala Ala Ala Ser Asp
Arg Ala Ser Asp Ala Ala1 5 10
15 cac cag gta tgc tgt tcc aac cct gtc tgt cac gtg gat cat cca
gaa 96His Gln Val Cys Cys Ser Asn Pro Val Cys His Val Asp His Pro
Glu 20 25 30 ctt tgt
cgt aga aga cgc tgatgctcca ggaccctctg aaccacgacg t 145Leu Cys
Arg Arg Arg Arg 35
39238PRTConus stercusmuscarum 392Ser Asp
Gly Arg Asn Ala Ala Ala Ser Asp Arg Ala Ser Asp Ala Ala 1
5 10 15 His Gln Val Cys Cys Ser
Asn Pro Val Cys His Val Asp His Pro Glu 20
25 30 Leu Cys Arg Arg Arg Arg
35
393154DNAConus striatusCDS(1)..(123) 393tct gat ggc agg aat
gcc gcg gcc aac gac aaa gcg tct gac ctg gtc 48Ser Asp Gly Arg Asn
Ala Ala Ala Asn Asp Lys Ala Ser Asp Leu Val1 5
10 15 gct ccg gcc atc agg gga tgc tgt tcc cac
cct gtc tgt aac ttg agt 96Ala Pro Ala Ile Arg Gly Cys Cys Ser His
Pro Val Cys Asn Leu Ser 20 25
30 aat cca caa att tgt cgt gga aga cgc tgatgctcca ggaccctctg
143Asn Pro Gln Ile Cys Arg Gly Arg Arg
35 40 aaccacgacg t
15439441PRTConus striatus
394Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Asp Leu Val 1
5 10 15 Ala Pro Ala Ile
Arg Gly Cys Cys Ser His Pro Val Cys Asn Leu Ser 20
25 30 Asn Pro Gln Ile Cys Arg Gly Arg
Arg 35 40
395117DNAConus textileCDS(1)..(114) 395ttt cat ggc
agg aat gcc gca gcc aaa gcg tct ggc ctg gtc ggt ctg 48Phe His Gly
Arg Asn Ala Ala Ala Lys Ala Ser Gly Leu Val Gly Leu1 5
10 15 acc gac aag agg caa gaa tgc tgt
tct cat cct gcc tgt aac gta gat 96Thr Asp Lys Arg Gln Glu Cys Cys
Ser His Pro Ala Cys Asn Val Asp 20 25
30 cat cca gaa att tgt cgt tga
117His Pro Glu Ile Cys Arg 35
39638PRTConus textile 396Phe His Gly Arg Asn Ala Ala Ala Lys Ala Ser Gly
Leu Val Gly Leu 1 5 10
15 Thr Asp Lys Arg Gln Glu Cys Cys Ser His Pro Ala Cys Asn Val Asp
20 25 30 His Pro
Glu Ile Cys Arg 35
397151DNAConus
tulipaCDS(1)..(120) 397act gat ggc agg agt gct gca gcc ata gcg ttt gcc
ctg atc gct ccg 48Thr Asp Gly Arg Ser Ala Ala Ala Ile Ala Phe Ala
Leu Ile Ala Pro 1 5 10
15 acc gtc tgg gaa gga tgc tgt tct aat cct gcc tgt ctc gtg aat cat
96Thr Val Trp Glu Gly Cys Cys Ser Asn Pro Ala Cys Leu Val Asn His
20 25 30 ata cgc ttt tgt
ggt gga aga cgc tgatgcccca ggaccctctg aaccacgacg 150Ile Arg Phe Cys
Gly Gly Arg Arg 35
40 t
15139840PRTConus tulipa 398Thr Asp Gly
Arg Ser Ala Ala Ala Ile Ala Phe Ala Leu Ile Ala Pro 1 5
10 15 Thr Val Trp Glu Gly Cys Cys
Ser Asn Pro Ala Cys Leu Val Asn His 20 25
30 Ile Arg Phe Cys Gly Gly Arg Arg
35 40
399157DNAConus virgoCDS(1)..(117) 399tct aat ggc atg aat gcc gca
gcc atc agg aaa gcg tct gcc ctg gtg 48Ser Asn Gly Met Asn Ala Ala
Ala Ile Arg Lys Ala Ser Ala Leu Val1 5 10
15 gct cag atc gcc cat cga gac tgc tgt gac gat cct
gcc tgc acc gtg 96Ala Gln Ile Ala His Arg Asp Cys Cys Asp Asp Pro
Ala Cys Thr Val 20 25 30
aat aat cca ggc ctt tgc act tgaagatgct gctgccccag gaccctctga
147Asn Asn Pro Gly Leu Cys Thr 35
accacgacgt
15740039PRTConus virgo 400Ser
Asn Gly Met Asn Ala Ala Ala Ile Arg Lys Ala Ser Ala Leu Val 1
5 10 15 Ala Gln Ile Ala His
Arg Asp Cys Cys Asp Asp Pro Ala Cys Thr Val 20
25 30 Asn Asn Pro Gly Leu Cys Thr
35
401154DNAConus geographusCDS(1)..(114) 401tct gat ggc ggg
aat gcc gca gca aaa gag tct gac gtg atc gct ctg 48Ser Asp Gly Gly
Asn Ala Ala Ala Lys Glu Ser Asp Val Ile Ala Leu1 5
10 15 acc gtc tgg aaa tgc tgt acc att cct
tcc tgt tat gag aaa aaa aaa 96Thr Val Trp Lys Cys Cys Thr Ile Pro
Ser Cys Tyr Glu Lys Lys Lys 20 25
30 att aaa gca tgt gtc ttt tgacgacgct gatgctccag gaccctctga
144Ile Lys Ala Cys Val Phe
35 accacgacgt
15440238PRTConus geographus
402Ser Asp Gly Gly Asn Ala Ala Ala Lys Glu Ser Asp Val Ile Ala Leu 1
5 10 15 Thr Val Trp Lys
Cys Cys Thr Ile Pro Ser Cys Tyr Glu Lys Lys Lys 20
25 30 Ile Lys Ala Cys Val Phe
35
403154DNAConus regiusCDS(1)..(114) 403tct gat ggc gca
gtc gac gac aaa gcg ttg gat cga atc gct gaa atc 48Ser Asp Gly Ala
Val Asp Asp Lys Ala Leu Asp Arg Ile Ala Glu Ile1 5
10 15 gtc agg aga gga tgc tgt ggc aat cct
gcc tgt agc ggc tcc tcg aaa 96Val Arg Arg Gly Cys Cys Gly Asn Pro
Ala Cys Ser Gly Ser Ser Lys 20 25
30 gat gca ccc tct tgt ggt tgaagacgct gctgctccag gaccctctga
144Asp Ala Pro Ser Cys Gly
35 accacgacgt
15440438PRTConus regius
404Ser Asp Gly Ala Val Asp Asp Lys Ala Leu Asp Arg Ile Ala Glu Ile 1
5 10 15 Val Arg Arg Gly
Cys Cys Gly Asn Pro Ala Cys Ser Gly Ser Ser Lys 20
25 30 Asp Ala Pro Ser Cys Gly
35
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