Composite materials

Abstract

This application discloses a composite material comprising one or more silk elements in an acrylic or cross-linked protein matrix. The silk elements are made from the group of silk elements consisting of domestic silkworm silk, wild silkworm silk, spider dragline silk, and filaments spun from recombinant silk protein or protein analogues. The composite material is particularly useful for use in-surgical-implants.

Description

FIELD OF THE INVENTION

[0001] The invention relates to a composite material comprising one or more silk elements in an acrylic or cross-lined protein matrix, its method of manufacture and its use in surgical implants.

BACKGROUND

[0002] Biodegradable polymer materials made of silk fibroin elements-are known, for example, from US-A-2004/0005363 (Tsukada et al.). This patent document teaches a composite material made from silk fibroin and another secondary substance, such as cellulose, chitin, chitosan (or derivatives), Keratin-or polyvinyl alcohol. The composite material can be used as a sustained release substrate for medicines, a biological cell growth substrate, a metal ion-absorbing material and a biodegradable water-absorbing material.

[0003] Another example of a composite material in which proteins coat the surface of a surgical device is disclosed in WO-A-94/22584 entitled "Chronic Endothelial Cell Culture under flow". In this patent application, the inner lumen of a hollow polypropylene fibre was coated with a synthetic protein polymer Fibronectin F which contains multiple repeats of the RGD fibronectin binding site. This produced an inner lumen surface which was substantially uniformly coated with the synthetic protein polymer on which cells could be grown. The polypropylene fibres can be used in vascular grafts. The strength of the vascular graft is as a result dependent on the tensile strength of the polypropylene fibres.

[0004] The surgical device (stent grafts and vascular grafts) described in WOA-01/38373 (Boston Scientific) exploits the strength of spider silk by providing an outer or interstitial sheath over the outside surface or the luminal surface of an inner stent The inner stent is made from a multitude of materials such as synthetic textile materials, fluoropolymers and polyolefines. Nylon, polyester and polyurethane are often used. These-materials which can not be resorbed by the body. The material of the outer sheath is non-resorbable conventional man-made polymeric material or a combination of spider silk and man made polymeric material.

SUMMARY OF THE INVENTION

[0005] These and other objects of the invention are solved by providing a composite material having one or more silk elements in an acrylic or cross-linked protein matrix. This material is highly biocompatible. Preferably the silk elements are made from wild silkworm silk, domestic silkworm silk spider-dragline silk, and filaments spun from recombinant silk protein or protein analogues or mixtures of these. A protein matrix is preferred because this means that both the protein matrix and the silk elements are resorbable.

[0006] In one embodiment of the invention, the silk elements are embedded in an acrylic matrix made of a cyanoacrylate, as this acrylate is known to be biocompatible. Alternatively, the silk elements can be incorporated into a matrix made of cross-linked fibroin or cross-linked casein.

[0007] In a particularly advantageous embodiment of the invention, the silk elements are made from the silk derived from wild silkworms (i.e. Tussah silk) as the resorbtion rate of the composite material formed from the cross-lined protein matrix and wild silkworm silk elements is slower than that of composite material with silk elements derived from spider silk.

[0008] In one embodiment of the invention, the silk elements formed from a plurality of short filaments with a staple-length less than 120 mm are from carded filaments (i.e. filaments drawn to lie approximately parallel to one another by a combing process). In another embodiment of the invention, the silk elements are twisted into a thread which call also be further twisted into a cord or rope or woven, braided, embroidered, wound, stitched or knitted.

[0009] The composite material can be formed into a substantially cylindrical form with the silk elements wound at an angle in excess of 40 degrees to the long axis of the substantially cylindrical form or circumferentially to the long axis. On a luminal surface of the form, the silk elements can be wound parallel to the long axis of the substantially cylindrical form. This latter construction has the advantage that it should stimulate longitudinal movement of nerve processes in a sleeve and therefore promote nerve regeneration.

[0010] Mineralisation of the composite material is advantageous as this allows the composite material to be used as a bone substitute and stimulates regrowth of the bone material.

[0011] The principal silk protein used in the silk elements contains at least eight repeats of the triplet RGD. The eight repeats of the triplet RGD are located immediately adjacent to turns or predicted turns of a structure of the principal silk protein. This is advantageous as this sequence when next to a turn specifically recognises and holds the fibronectin binding site of integrin molecules anchored to the surface of most metazoan cell types. In turn this leads to excellent cell adhesion and advantageous changes in cell physiology including polarisation of function, cell differentiation and changes in the cell cycle.

[0012] The composite material is in one use formed into surgically implantable devices, such as sutures, artificial ligaments and tendons, endoluminar devices, anastomosis devices, and sleeves to aid in the regeneration of nerve cells

[0013] The invention also comprises a method for the manufacture of a compound material with a first step of providing one or more silk elements and a second step of embedding the silk element in an acrylic or protein matrix. The silk elements can be obtained by degumming and unwinding or combing silk from a cocoon.

[0014] Fibroin can be prepared for the protein matrix by dissolving domestic or wild silkworm silk or cocoons in one or more chaotropic agents, such as calcium nitrate solution and lithium thiocyanate solution.

[0015] The protein matrix is cross-linked using a cross-linking agent such as formaldehyde vapour, glutaraldehyde, polyglutaraldehyde, carbodiimide and genipin.

[0016] The acrylic or fibroin material is applied to the silk elements by dipping, painting, spraying or casting.

[0017] An apparatus for the manufacture of an object made from the composite material is also part of the invention. The apparatus has a storage region having silk elements,-a substantially cylindrical former and finally a feeding means to place said silk elements about the former.

[0018] The feeding means comprises rollers and tension is maintained between the rollers and the former to pre-stress and straighten the silk elements so as to ensure a good final product.

[0019] In one embodiment of the invention, a take up drum is used to form an object which is then removed as a substantially cylindrical form from the take up drum. Advantageously, cared silk fibres are fed to a cylindrical former and continuously coated onto the substantially cylindrical drum and finally a composite sheet emerges continuously from the substantially cylindrical drum.

DESCRIPTION OF THE DRAWINGS

[0020] FIG. 1 shows a composite material according to this invention.

[0021] FIG. 2 shows a first manufacturing method for the composite material.

[0022] FIG. 3 shows a second manufacturing method for the composite material.

[0023] FIG. 4 shows the distribution of the fibronectin binding triplet RGD in the repetitive part of the sequence of Antheraea pernyi (left column) and A. yamamai (right column) heavy chain fibroin.

[0024] FIG. 5 shows the consensus repeat sequence for the glycine-rich domains for the first 900 repetitive amino acids of the repetitive region of A. pernyii heavy chain fibroin.

[0025] FIG. 6 shows the position of a putative turn immediately adjacent to the RGD triplet in the consensus sequence from the glycine-rich domain of A. pernyi heavy chain fibroin.

DETAILED DESCRIPTION OF THE INVENTION

[0026] FIG. 1 shows a composite material 30 comprising one or more silk elements 10 in a matrix material 20. The matrix material 20 can be an acrylic matrix, made for example from a cyanoacrylate, or a protein matrix. The protein matrix can, for example, be a fibroin matrix or a casein matrix. Other highly soluble proteins could also be used. The protein matrix is cross-lined using a cross-liking agent such as formaldehyde vapour glutaraldehyde, polyglutaraldehyde, formaldehyde carbodiimide and genipin. In one embodiment the protein matrix is cross-lined by heating substantially dry formaldehyde vapour generated by heating paraformaldehyde in a sealed container to 80-100 degrees centigrade for 5 minutes to 3 hours.

[0027] The silk elements 10 are made from domestic silkworm soil, wild silkworm silk or spider dragline silk The silk elements 10 could also be made from recombinant silk protein or protein analogues. The silk elements 10 produced from wild silkworm in general means those elements produced by Antheraea pernyi, Antheraea yamamai, Antheraea militta, Antheraea assama, Philosamia Cynthia ricini and Philosamia Cynthia pryeri. The silk of other Saturnid moths such as those of the genus Actias or Cecropia though not generally defined as wild silk worms yield a closely similar silk element and can be used in this invention as the silk elements 10.

[0028] In FIG. 1 a simple block of composite material 30 is known. However, other shapes are possible such as fibres, rods, sheets or tubes as will become clear from the discussion below.

[0029] The silk elements 10 can be made up of a plurality of silk elements which have been twisted together to form a thread. The silk elements 10 can be further made of a plurality of short filaments of silk, for example with a staple length as long as possible and at least 20 mm. The silk elements 10 can be twisted into pairs or multiples to form a thread which can also be further twisted into a cord or rope or woven, braided, embroidered, wound, stitched or knitted to form devices. In one advantageous embodiment of the invention, the silk elements 10 comprise carded filaments.

[0030] In one embodiment of the invention, the silk elements 10 are degummed from the silk cocoon. However, other methods of extracting the silk elements 10 can be used.

[0031] The fibroin for the protein matrix 20 is extracted by dissolving domestic or wild silkworm silk or cocoons in one or more chaotropic agents, such as calcium nitrate solution and lithium thiocyanate solution. In the case of wild sills, it is necessary to heat the chaotropic agent. The silk elements 10 are placed in the resultant solution-which is then dialysed to remove the chaotropic agent or agents and concentrated or dried by evaporation or reverse dialysis. The concentrated fibroin solution can be dried into films or flakes for storage and redissolved in distilled water or other solvents when required.

[0032] US Patent U.S. Pat. No. 5,245,012 (US Army) also teaches a method of dissolving silk protein extracted from different arachnid species using varying solvent systems. The teachings of this patent are incorporated herein by reference.

[0033] The composite material 30 of the invention can be used to make a variety of objects. One example of an apparatus for the manufacture of the objects 100 is shown in FIG. 2 in which the silk elements 10 are initially held in a storage region 200 and are spooled (or otherwise fed) to a drum 210 over rollers 220 and wrapped circumferentially or helically about the drum 210. The function of the rollers 220 is to ere that the silk elements 10 are pre-stressed and therefore firmly placed on the drum 210. The matrix material 20 is then coated by an application device 250 over the outer surface 240 of the drum 210 with matrix material 20 to affix and embed the silk elements 10. It will be understood that the drum 210 could also be a mandrel or more generally a former. It will be understood that the silk elements 10 can be laid down on the drum 210 or mandrel in many different patterns of orientation by rotating the drum 210 or mandrel and changing the spatial relationship between the drum 210 and the rollers 220.

[0034] In a further embodiment a composite rope or cable structure is formed as follows. Two or more lengths of single, double or multiple ply silk threads-are twisted into a thin rope. The acrylate or fibroin solutions for the matrix can be applied before or after twisting. After drying or partial drying, the matrix is then cross-linked by chemical treatment, preferably by hot formaldehyde vapour. It will be understood that by successive twisting varying hierarchical levels of construction to give cords, ropes or cables of thicknesses appropriate to end use. The resulting materials can be incorporated into a variety of prosthetic devices including-tendon and ligament prostheses or embroidered or knitted devices.

[0035] The object 30 constructed in accordance with the teas of FIG. 2 can be advantageously made with silk elements 10 formed from carded silk filaments derived from silk brins. Carded silk filaments are very thin (30 μm diameter) allowing the manufacture of thin-walled devices or composite sheets.

[0036] The drum 210 can be so arranged that a continuous sheet made of composite material 30 emerges from the drum 210 as shown in the FIG. 2.

[0037] As the composite material 30 is biocompatible, it can be used to make an implant, such as an endolumnal device, a stent device, an anastomosis is device, a sure, or a device to promote nerve regeneration. It is known that the silk elements 10 provide an excellent substrate for cell or tissue growth. Therefore some of the matrix material 20 of the object 100 can be abraded away to reveal some of the silk elements 10 on either an inner (or endolumnal) surface 230 of the object 30 or on an outer surface 240 of the object 30.

[0038] Another method for the manufacture of the object 30 in a tubular structure is shown in FIG. 3 in which silk elements 10 are wrapped substantially longitudinally along the surface of a former 300 on both an inner surface 310 and an outersurface 320 of the former 300. The former has typically a diameter between 0.5 mm but can have a diameter up to 10 m and has a long axis 325. The former 300 could also be tapered. The matrix material 20 is applied over the silk elements 10 and allowed to dry and thus embed the silk elements 10 in the object. Application of the materials by dipping, painting, spraying or casting. The ends 330a and 330b of the object 30 can be cut away and the former 300 slipped out. A tubular object is thus created. Formers coated with a layer of wax or which can be caused to collapse into a smaller diameter can be used to facilitate removal of the object 30 from the former 300.

EXAMPLES

Example 1

Preparation of Composite Materials from Carded Antheraea Pernyii Silk Filaments.

[0039] Antheraea pernyii silk filaments prepared from degummed silk cocoons were obtained from a commercial supplier. The carded silk from the sepin was smoothed into flat sheets and gently tensioned to pull the silk filaments parallel. Keeping the silk tensioned they were wound on to cylindrical formers 0.25 mm to 30 mm in diameter. The largest cylinders were made of glass and had a substantially smooth surface. The Smallest cylinders 0.25 mm were prepared by coating a thin stiff wire in low melting point wax. Cylindrical formers with intermediate diameters were made from low melting point wax. The silk filaments were generally laid circumferentially on the largest formers but were laid in a helical fashion on the smaller cylindrical formers.

[0040] Care was taken to ensure a uniform dense lay of filaments was achieved on the cylindrical formers. The silk filaments at the ends of the thin cylindrical formers were secured with cyanoacrylate adhesive from Loctite. For the larger cylindrical formers the silk filaments at the ends were secured by a thin line of superglue running parallel to the long axis of the cylindrical former. This allows the removal of the composite material from the cylindrical former making a cut along the thin line of adhesive.

[0041] The composite material was formed either by painting a thin coat of either cyanoacrylate adhesive or concentrated regenerated fibroin solution on to the silk filaments. The regenerated fibroin solution was prepared by dissolving commercial degummed Bombyx mori fibroin powder in aqueous 63 M lithium bromide with gentle stirring at room temperature. The silk solution was then dialysed in 18-20 kDa MWCO Visking tubes with two changes for a total of 6 hours at 4 degrees-centigrade against aqueous 0.5M lithium bromide solution with the intention of allowing the protein to refold after dissolution in the concentrated lithium bromide. Thereafter water was removed from the fibroin solution by reverse dialysis against aqueous 40% aqueous--or dry-powdered polyethylene glycol-(MW 15-20 kDa), pooling the partially concentrated fibroin after 12 hours--24 hours of dialysis to a fresh dialysis tube to obtain a final highly concentrated solution. Alternatively the dialysed silk fibroin solution was allowed to partially dry by exposing the sealed the dialysis bag to dry air. The matrix material was applied by painting the concentrated fibroin onto the silk filaments and allowed to dry. Thereafter the matrix was cross-linked by treatment with substantially dry formaldehyde gas by heating to 80-100 degrees centigrade for 5 minutes to 3 hours in a sealed vessel containing substantially dry paraformaldehyde. Unreacted formaldehyde was removed by heating the material to 100 degrees centigrade in a stream of air or by exhaustive washing.

[0042] Testing of the composite materials for mechanical strength was carried out by cutting silk acrylate strips made using the larger cylindrical formers as described below in Example 3. An Instron universal mechanical testing instrument fitted with pneumatic grips was used to test composite strips to failure in uniaxial tension parallel to the lay of the silk filaments.

Example 2

Demonstration of RGD Putative Integrin Binding Sites on Antheraea spp Heavy Chain Fibroins and their Location Adjacent to Turns.

[0043] The published sequences of silk proteins were searched on the TrBMBL and SwissPROT data bases for the well established cell binding sequence RGD and the putative cell binding sites PPSRN and KNEED. The sequence triplet RGD is of considerable interest as it forms part of the mechanism used in multicellular organisms to stick many types of cells to the connective tissue framework of the body. The RGD triplet on the silk-like connective tissue protein fibronectin binds specifically to integrins. Integrins are a class of cell adhesion molecules. They are found intercalated into the lipid bilayer of the cell membrane with the fibronectin binding (RGD recognition) site protruding into the extracellular space. Thus the RGD recognition site of integrins is available-to bind cells to the connective tissue-framework via RGD triplets on fibronectin molecules.

[0044] The putative cell binding sites PPSRN and KNEED were absent from all silks examined. However, multiple copies of the triplet RGD were found in the glycine rich domains of thee heavy chain fibroins of Antheraea pernyi (TrEMBL O76786), A. yamamai (TrEMBL Q964F4) and A. militta (Q8ISB3). There were 12-and 14 repeats respectively in the complete sequence of A. pernyii and A. yamana and an even higher density of repeats (7) in the partial sequence-of A. miitta. Then remarkably repetitive location of the RGD repeats is shown for A. pernyii in FIG. 4. The RGD motif recurs in a constant location, in the glycine-rich repeat immediately separated by one polyalanine repeat before the sequence SAARRAGHDRAAGS (sometimes truncated to RRAGHDRAAGS) or a closely similar sequence.

[0045] In all cases the RGD triplet immediately preceded the motif GGYG. A. militta differed from the two other Antheraea sp in having two RGD's instead of one in one of its glycine-rich domains.

[0046] The RGD triplet was absent from all other silk protein sequences examined with the exception of that for Samia ricini heavy chain fibroin which contained a single copy immediately preceding a YGSD motif in a glycine-rich domain close to the end of this very long sequence.

[0047] Thus the cell-binding sequence RGD is found in multiple copies in the heavy chain fibroins of three Anthemea species.

[0048] We then sought to discover if the RGD sequence is present in locations within the silk molecule likely to be accessible to cell surface integrins. To seek an answer to this we first used RADAR (Expasy tools) to determine the consensus sequence for the repetitive glycine rich domains of Antheraea pernyii heavy chain fibroin (see FIG. 5).

[0049] This showed that the sequence GGYGXGDGGYGSDS (where X=W or R) was well conserved within the glycine-rich domains. We then used a sophisticated secondary structure prediction tool, SCRATCH (Expasy tools) to determine the location of a putative turn within the consensus sequence (see FIG. 6), as previous research (Peng et al. 2004 in preparation) has shown that tons are present within silk molecules as part of a tertiary structure defined by the existence of antiparallel β-sheets. A turn in the A. pernyi consensus sequence was found to be centered on a glycine residue immediately adjacent to the RGD. As each RGD triplet in fibronectin are located immediately adjacent to a turn (Leahy, Hendrickson et al. 1992; Leahy, Aukbil et al. 1996). We conclude that the RGD in Antheraea silks is likely to be available for binding to integrins and is therefore likely to strongly promote cell adhesion to this silk

Example 3

[0050] Tensile Data on Antheraea Pernyi Cyanoacrylate Composite TABLE-US-00001 TABLE 1 Tensile test data (n = 6) for wet strips of composite material containing a high density of well-oriented Antheraea pernyii filaments set in a cyanoacrylate matrix. The strips (50 mm gauge length, average width 10.5 mm and thickness 0.4 mm) were strained parallel to the filament orientation UTS (Mpa) Strain to failure Energy/kg (JKg) Modulus (Mpa) Average: 31 0.150 1900 1000 SD 8.080 0.016 590 227

[0051] For comparison, the ultimate tensile stress of a typical-low alloy steel is in the region of 830 Mpa and a modulus of 200 Mpa but steel has a density of approximately 6 times that of the silk composite thus weight for weight this steel is less than 4 times as strong as the silk composite. The tensile data for the silk composite are comparable with that of that of two synthetic implantable materials (table 2). TABLE-US-00002 TABLE 2 Tensile data for wild silk cyanoacrylate composite compared with two synthetic implantable materials. Poly ε A. pernyi acrylate Property Poly-L-lactide caprolactone composite Ultimate tensile 45 MPa 22 MPa 31 MPa strength Ultimate extension 3% 500% 16% Initial modulus 2.7 GPa 0.4 GPa 1 GPa

[0052]

Sequence CWU 1

187 1 5 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 1 Pro Pro Ser Arg Asn 1 5 2 5 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 2 Lys Asn Glu Glu Asp 1 5 3 14 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 3 Ser Ala Ala Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser 1 5 10 4 11 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 4 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser 1 5 10 5 4 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 5 Gly Gly Tyr Gly 1 6 4 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 6 Tyr Gly Ser Asp 1 7 14 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide MOD_RES (5)..(5) Trp or Arg 7 Gly Gly Tyr Gly Xaa Gly Asp Gly Gly Tyr Gly Ser Asp Ser 1 5 10 8 2000 PRT Antheraea pernyi 8 Met Arg Val Ile Ala Phe Val Ile Leu Cys Cys Ala Leu Gln Tyr Ala 1 5 10 15 Thr Ala Lys Asn Leu Arg His His Asp Glu Tyr Val Asp Asn His Gly 20 25 30 Gln Leu Val Glu Arg Phe Thr Thr Arg Lys His Phe Glu Arg Asn Ala 35 40 45 Ala Thr Arg Pro His Leu Ser Gly Asn Glu Arg Leu Val Glu Thr Ile 50 55 60 Val Leu Glu Glu Asp Pro Tyr Gly His Glu Asp Ile Tyr Glu Glu Asp 65 70 75 80 Val Val Ile Lys Arg Val Pro Gly Ala Ser Ser Ser Ala Ala Ala Ala 85 90 95 Ser Ser Ala Ser Ala Gly Ser Gly Gln Thr Ile Ile Val Glu Arg Gln 100 105 110 Ala Ser His Gly Ala Gly Gly Ala Ala Gly Ala Ala Ala Gly Ala Ala 115 120 125 Ala Gly Ser Ser Ala Arg Arg Gly Gly Gly Phe Tyr Glu Thr His Asn 130 135 140 Ser Tyr Ser Ser Tyr Gly Ser Gly Ser Ser Ser Ala Ala Ala Gly Ser 145 150 155 160 Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala 165 170 175 Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly 180 185 190 Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala 195 200 205 Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly 210 215 220 Gly Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala 225 230 235 240 Ala Ala Ala Ala Ala Ala Gly Ser Ser Ala Gly Gly Ala Gly Gly Gly 245 250 255 Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala 260 265 270 Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Ser 275 280 285 Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala 290 295 300 Ala Ala Ala Ala Ala Ala Ala Gly Ser Ser Ala Gly Gly Ala Gly Gly 305 310 315 320 Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala 325 330 335 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Ser Gly Ala Gly Gly Arg 340 345 350 Gly Asp Gly Gly Tyr Gly Ser Gly Gly Ser Ser Ala Ala Ala Ala Ala 355 360 365 Ala Ala Ala Ala Ala Ala Ala Arg Arg Ala Gly His Asp Arg Ala Ala 370 375 380 Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser 385 390 395 400 Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr 405 410 415 Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 420 425 430 Ala Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp 435 440 445 Ser Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala 450 455 460 Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr 465 470 475 480 Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 485 490 495 Ala Gly Ala Gly Ala Gly Gly Ala Gly Gly Ser Tyr Gly Trp Gly Asp 500 505 510 Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala 515 520 525 Ala Ala Ala Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly 530 535 540 Ser Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Ala 545 550 555 560 Ala Arg Arg Ala Gly His Asp Ser Ala Ala Gly Ser Ala Ala Ala Ala 565 570 575 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly 580 585 590 Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala 595 600 605 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly 610 615 620 Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp 625 630 635 640 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly 645 650 655 Ala Arg Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala 660 665 670 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly 675 680 685 Gly Val Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp 690 695 700 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly 705 710 715 720 Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala 725 730 735 Ala Ala Ala Ala Ala Ala Ala Ala Ser Ala Ala Arg Arg Ala Gly His 740 745 750 Asp Ser Ala Ala Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 755 760 765 Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly 770 775 780 Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala 785 790 795 800 Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr 805 810 815 Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala 820 825 830 Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Arg Gly Ser Gly Gly 835 840 845 Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala 850 855 860 Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr 865 870 875 880 Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala 885 890 895 Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Arg Gly Asp 900 905 910 Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala 915 920 925 Ala Ala Ser Ala Ala Arg Arg Ala Gly His Asp Ser Ala Ala Gly Ser 930 935 940 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala 945 950 955 960 Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser 965 970 975 Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly 980 985 990 Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 995 1000 1005 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1010 1015 1020 Ala Ala Ala Ser Gly Ala Arg Gly Ser Gly Gly Tyr Gly Gly Tyr 1025 1030 1035 Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1040 1045 1050 Ala Ala Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Trp 1055 1060 1065 Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala 1070 1075 1080 Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Arg Gly Asp 1085 1090 1095 Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala 1100 1105 1110 Ala Ala Ala Ala Ala Arg Arg Ala Gly His Asp Arg Ala Ala Gly 1115 1120 1125 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser 1130 1135 1140 Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1145 1150 1155 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1160 1165 1170 Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly 1175 1180 1185 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1190 1195 1200 Ala Ala Ala Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly 1205 1210 1215 Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala 1220 1225 1230 Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly 1235 1240 1245 Gly Tyr Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala 1250 1255 1260 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly 1265 1270 1275 Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser 1280 1285 1290 Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly 1295 1300 1305 Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1310 1315 1320 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Arg 1325 1330 1335 Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1340 1345 1350 Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly 1355 1360 1365 Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala 1370 1375 1380 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly 1385 1390 1395 Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser Ala 1400 1405 1410 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly 1415 1420 1425 Ala Gly Gly Val Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr 1430 1435 1440 Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1445 1450 1455 Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr Gly 1460 1465 1470 Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1475 1480 1485 Ala Ala Ser Gly Ala Gly Gly Ala Gly Gly Tyr Gly Gly Tyr Gly 1490 1495 1500 Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1505 1510 1515 Ala Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly 1520 1525 1530 Asp Gly Gly Tyr Gly Ser Tyr Ser Ala Ala Ala Ala Ala Ala Ala 1535 1540 1545 Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly 1550 1555 1560 Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala 1565 1570 1575 Ala Ala Ala Ala Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser 1580 1585 1590 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly 1595 1600 1605 Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr 1610 1615 1620 Ser Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1625 1630 1635 Ala Ala Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp 1640 1645 1650 Gly Asp Asp Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala 1655 1660 1665 Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Arg Gly Gly 1670 1675 1680 Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala 1685 1690 1695 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly 1700 1705 1710 Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala 1715 1720 1725 Ala Ala Ala Ala Ala Ala Ala Ala Ala Arg Arg Ala Gly His Asp 1730 1735 1740 Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1745 1750 1755 Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly Ser Tyr Gly Trp Gly 1760 1765 1770 Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala 1775 1780 1785 Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly Tyr 1790 1795 1800 Gly Gly Tyr Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala 1805 1810 1815 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser 1820 1825 1830 Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1835 1840 1845 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1850 1855 1860 Ala Ala Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly 1865 1870 1875 Ser Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1880 1885 1890 Ala Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala 1895 1900 1905 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly 1910 1915 1920 Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp 1925 1930 1935 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly 1940 1945 1950 Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Asp 1955 1960 1965 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala 1970 1975 1980 Ala Ala Ala Gly Ser Gly Ala Gly Gly Arg Gly Gly Gly Tyr Gly 1985 1990 1995 Trp Gly 2000 9 2655 PRT Antheraea yamamai 9 Met Arg Val Thr Ala Phe Val Ile Leu Cys Cys Ala Leu Gln Tyr Ala 1 5 10 15 Thr Ala Asn Asn Leu His His His Asp Glu Tyr Val Asp Asn His Gly 20 25 30 Gln Leu Val Glu Arg Phe Thr Thr Arg Lys His Tyr Glu Arg Asn Ala 35 40 45 Ala Thr Arg Pro His Leu Ser Gly Asn Glu Arg Leu Val Glu Thr Ile 50 55 60 Val Leu Glu Glu Asp Pro Tyr Gly His Glu Asp Ile Tyr Glu Glu Asp 65 70 75 80 Val Val Ile Asn Arg Val Pro Gly Ala Ser Ser Ser Ala Ala Ala Ala 85 90 95 Ser Ser Ala Ser Ala Gly Ser Gly Gln Thr Ile Ile Val Glu Arg Gln 100 105 110 Ala Ser His Gly Ala Gly Gly Ala Ala Gly Ala Ala Ala Gly Ala Ala 115 120 125 Ala Gly Ser Ser Ala Arg Gly Gly Ser Gly Phe Tyr Glu Thr His Asp 130 135 140 Ser Tyr Ser Ser Tyr Gly Ser Gly Ser Ser Ser Ala Ala Ala Ala Ser 145 150 155 160 Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 165 170 175 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 180 185 190 Ala Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly 195 200 205 Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Arg Arg 210 215 220 Ala Gly His Asp His Ala Ala Gly Ser Ser Gly Gly Gly Tyr Ser Trp 225 230 235 240 Asp Tyr Ser Ser Tyr Gly Ser Glu Ser Ala Ala Ala Ala Ala Ala Ala 245 250 255 Ala Ala Ala Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Gly 260 265 270 Gly Asp Gly

Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala Ala Ala Ala 275 280 285 Ala Ala Ala Ala Ala Ala Arg Arg Ala Gly His Asp Arg Ala Ala Gly 290 295 300 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly 305 310 315 320 Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly 325 330 335 Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 340 345 350 Gly Ser Gly Ala Gly Arg Ala Gly Gly Asp Tyr Gly Trp Gly Asp Gly 355 360 365 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 370 375 380 Ala Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly 385 390 395 400 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 405 410 415 Ala Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly 420 425 430 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 435 440 445 Ala Ala Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser 450 455 460 Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 465 470 475 480 Arg Gln Ala Gly His Glu Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 485 490 495 Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly Arg 500 505 510 Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala 515 520 525 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly 530 535 540 Ala Gly Gly Asp Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser 545 550 555 560 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly 565 570 575 Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser 580 585 590 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala 595 600 605 Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala 610 615 620 Ala Ala Ala Ala Ala Ala Ala Ala Ala Arg Arg Ala Gly His Asp Arg 625 630 635 640 Ala Ala Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 645 650 655 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 660 665 670 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 675 680 685 Ala Ala Gly Ser Gly Ala Gly Gly Ala Gly Gly Asp Tyr Gly Trp Gly 690 695 700 Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala 705 710 715 720 Ala Ala Ala Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly 725 730 735 Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala 740 745 750 Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr 755 760 765 Gly Ser Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 770 775 780 Ala Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala 785 790 795 800 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly 805 810 815 Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala 820 825 830 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly 835 840 845 Gly Ala Gly Gly Asp Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp 850 855 860 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly 865 870 875 880 Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp 885 890 895 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly 900 905 910 Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala 915 920 925 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Arg Arg Ala Gly His Asp 930 935 940 Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 945 950 955 960 Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp 965 970 975 Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala 980 985 990 Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Ala Gly Gly Asp Tyr Gly 995 1000 1005 Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala 1010 1015 1020 Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ala Gly Gly Gly 1025 1030 1035 Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala 1040 1045 1050 Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly 1055 1060 1065 Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala Ala 1070 1075 1080 Ala Ala Ala Ala Ala Ala Ala Ala Arg Arg Ala Gly His Asp Arg 1085 1090 1095 Ala Ala Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1100 1105 1110 Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly 1115 1120 1125 Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala 1130 1135 1140 Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Val Gly Gly 1145 1150 1155 Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala 1160 1165 1170 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly 1175 1180 1185 Gly Ala Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala 1190 1195 1200 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Ser Gly Ala Gly 1205 1210 1215 Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser 1220 1225 1230 Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly 1235 1240 1245 Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1250 1255 1260 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser 1265 1270 1275 Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1280 1285 1290 Tyr Gly Ser Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1295 1300 1305 Ala Ala Ala Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly 1310 1315 1320 Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala 1325 1330 1335 Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ala Gly 1340 1345 1350 Gly Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala 1355 1360 1365 Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Ala Gly 1370 1375 1380 Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala 1385 1390 1395 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala 1400 1405 1410 Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala 1415 1420 1425 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Arg Arg Ala Gly Tyr 1430 1435 1440 Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala 1445 1450 1455 Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly 1460 1465 1470 Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala 1475 1480 1485 Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ala Gly 1490 1495 1500 Gly Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala 1505 1510 1515 Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Ala Gly 1520 1525 1530 Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala 1535 1540 1545 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala 1550 1555 1560 Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala 1565 1570 1575 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Arg Arg Ala Gly Tyr 1580 1585 1590 Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala 1595 1600 1605 Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly 1610 1615 1620 Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala 1625 1630 1635 Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ala Gly 1640 1645 1650 Gly Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala 1655 1660 1665 Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Ala Gly 1670 1675 1680 Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala 1685 1690 1695 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala 1700 1705 1710 Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala 1715 1720 1725 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Arg Arg Ala Gly 1730 1735 1740 His Asp Arg Ala Ala Gly Cys Ala Ala Ala Ala Ala Ala Ala Ala 1745 1750 1755 Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly 1760 1765 1770 Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala 1775 1780 1785 Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Ala 1790 1795 1800 Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser 1805 1810 1815 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly 1820 1825 1830 Gly Thr Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser 1835 1840 1845 Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly 1850 1855 1860 Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr 1865 1870 1875 Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1880 1885 1890 Ala Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser 1895 1900 1905 Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1910 1915 1920 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala 1925 1930 1935 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser 1940 1945 1950 Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asn Ser 1955 1960 1965 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser 1970 1975 1980 Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1985 1990 1995 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 2000 2005 2010 Ala Ala Ala Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly 2015 2020 2025 Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala 2030 2035 2040 Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Arg Gly 2045 2050 2055 Asp Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala Ala Ala Ala 2060 2065 2070 Ala Ala Ala Ala Ala Ala Arg Arg Ala Gly His Asp Arg Ala Ala 2075 2080 2085 Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 2090 2095 2100 Ser Gly Ala Gly Arg Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly 2105 2110 2115 Gly Tyr Ser Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala 2120 2125 2130 Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr 2135 2140 2145 Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala 2150 2155 2160 Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly 2165 2170 2175 Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala 2180 2185 2190 Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Val Gly Gly 2195 2200 2205 Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala 2210 2215 2220 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser 2225 2230 2235 Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala 2240 2245 2250 Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Val 2255 2260 2265 Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Gly Tyr Gly 2270 2275 2280 Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly 2285 2290 2295 Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Arg Gly Asp Ser 2300 2305 2310 Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala 2315 2320 2325 Ala Ala Ala Arg Arg Ala Gly His Gly Arg Ser Ser Gly Ser Ala 2330 2335 2340 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala 2345 2350 2355 Gly Gly Ser Gly Gly Gly Tyr Gly Trp Asp Tyr Gly Ser Tyr Gly 2360 2365 2370 Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 2375 2380 2385 Ser Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Asp Tyr 2390 2395 2400 Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala 2405 2410 2415 Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr 2420 2425 2430 Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala 2435 2440 2445 Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Arg 2450 2455 2460 Gly Asp Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala Ala Ala 2465 2470 2475 Ala Ala Ala Ala Ala Ala Ala Arg Arg Ala Gly His Asp His Ala 2480 2485 2490 Ala Gly Ser Ser Gly Gly Gly Tyr Ser Trp Asp Tyr Ser Ser Tyr 2495 2500 2505 Gly Ser Glu Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly 2510 2515 2520 Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Gly Gly Asp Gly 2525 2530 2535 Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala 2540 2545 2550 Ala Ala Ala Ala Ser Arg Arg Ala Gly His Asp Arg Ala Tyr Gly 2555 2560 2565 Ala Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ala 2570 2575 2580 Gly Ala Ser Arg Pro Val Gly Ile Tyr Gly Thr Asp Asp Gly Phe 2585 2590 2595 Val Leu Asp Gly Gly Tyr Asp Ser Glu Gly Ser Ala Ala Ala Ala 2600 2605 2610 Ala Ala Ala Ala Ala Ala Ala Ala Ser Ser Ser Gly Arg Ser Thr 2615 2620 2625 Glu Gly His Pro Leu Leu Ser Ile Cys Cys Arg Pro Cys Ser His 2630 2635 2640 Arg His Ser Tyr Glu Ala Ser Arg Ile Ser Val His 2645 2650 2655 10 507 PRT Antheraea militta 10 Met Arg Val Ile Ala Phe Val Ile Leu Cys Cys Ala Leu Gln Tyr Ala 1 5 10 15 Thr Ala Lys Asn Ile His His Asp Glu Tyr Val Asp Ser His Gly Gln

20 25 30 Leu Val Glu Arg Phe Thr Thr Arg Lys His Tyr Glu Arg Asn Ala Ala 35 40 45 Thr Arg Pro His Leu Ser Gly Asn Glu Arg Leu Val Glu Thr Ile Val 50 55 60 Leu Glu Glu Asp Pro Tyr Gly His Glu Asp Ile Tyr Glu Glu Asp Val 65 70 75 80 Val Ile Lys Arg Val Pro Gly Ala Ser Ser Ser Ala Ala Ala Ala Ser 85 90 95 Ser Ala Ser Ala Gly Ser Gly Gln Thr Ile Thr Val Glu Arg Gln Ala 100 105 110 Ser His Gly Ala Gly Gly Ala Ala Gly Ala Ala Ala Gly Ala Ala Ala 115 120 125 Ser Ser Ser Val Arg Gly Gly Gly Gly Phe Tyr Glu Thr His Asp Ser 130 135 140 Tyr Ser Ser Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala 145 150 155 160 Ala Ser Gly Ala Gly Gly Arg Gly His Gly Gly Tyr Gly Ser Asp Ser 165 170 175 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser 180 185 190 Gly Ala Gly Gly Arg Gly His Gly Gly Tyr Gly Ser Asp Ser Ala Ala 195 200 205 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala 210 215 220 Gly Gly Arg Gly Asp Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly 225 230 235 240 Ser Asp Ser Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 245 250 255 Ala Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Arg Gly Asp 260 265 270 Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala 275 280 285 Ala Ala Ala Gly Ser Gly Ala Gly Gly Gln Ala Thr Val Val Met Asp 290 295 300 Gly Ala Met Ala Ala Met Val Leu Thr Arg Ala Gln Gln Gln Leu Ala 305 310 315 320 Ala Ala Ala Ala Ala Ala Ser Ala Ser Gly Ala Gly Gly Ser Gly Gly 325 330 335 Ser Tyr Glu Trp Asp Tyr Gly Ser Tyr Gly Ser Asp Ser Ala Ala Ala 340 345 350 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly 355 360 365 Val Gly Gly Gly Tyr Gly Arg Gly Asp Gly Gly Tyr Gly Ser Asp Ser 370 375 380 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala 385 390 395 400 Gly Gly Arg Gly Asp Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly 405 410 415 Ser Asp Ser Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 420 425 430 Ala Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Trp Gly Asp 435 440 445 Gly Gly Tyr Gly Ser Asp Pro Gly Ala Ala Ala Ala Ala Ala Ala Ala 450 455 460 Ala Ala Ala Ala Ala Ser Gly Ala Arg Gly Arg Gly Asp Gly Gly Tyr 465 470 475 480 Gly Ser Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 485 490 495 Ser Ala Ala Arg Arg Ala Gly His Asp Arg Ala 500 505 11 9 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 11 Ala Gly Ala Ala Ala Gly Ala Ala Ala 1 5 12 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 12 Gly Ser Ser Ala Arg Arg Gly Gly Gly Phe Tyr Glu Thr His Asn Ser 1 5 10 15 Tyr Ser Ser Tyr Gly Ser Gly Ser Ser Ser Ala Ala Ala 20 25 13 25 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 13 Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Ser Asp Ser Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 14 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 14 Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 15 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 15 Gly Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Gly Tyr 1 5 10 15 Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 16 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 16 Gly Ser Ser Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Asp Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 17 30 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 17 Gly Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Ser Asp 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 18 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 18 Gly Ser Ser Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Asp Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 19 30 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 19 Ser Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Gly 1 5 10 15 Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 20 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 20 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 21 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 21 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 22 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 22 Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 23 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 23 Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 24 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 24 Gly Ala Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 25 27 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 25 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 26 27 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 26 Ser Ala Ala Arg Arg Ala Gly His Asp Ser Ala Ala Gly Ser Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 27 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 27 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 28 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 28 Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 29 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 29 Ser Gly Ala Arg Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 30 Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 31 27 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 31 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 32 27 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 32 Ser Ala Ala Arg Arg Ala Gly His Asp Ser Ala Ala Gly Ser Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 33 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 33 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 34 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 34 Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 35 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 35 Ser Gly Ala Arg Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 36 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 36 Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 37 27 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 37 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 38 27 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 38 Ser Ala Ala Arg Arg Ala Gly His Asp Ser Ala Ala Gly Ser Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 39 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 39 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 40 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 40 Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 41 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 41 Ser Gly Ala Arg Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 42 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 42 Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 43 27 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 43 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 44 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 44 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 45 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 45 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 46 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 46 Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 47 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 47 Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Ser 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 48 32 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 48 Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Gly Tyr Gly 1 5 10 15 Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 49 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 49 Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 50 27 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 50 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 51 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 51 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 52 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 52 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 53 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 53 Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 54 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 54 Gly Ser Gly Ala Gly Gly Ala Gly Gly Val Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 55 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 55 Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 56 28 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 56 Ser Gly Ala Gly Gly Ala Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala

20 25 57 27 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 57 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 58 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 58 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 59 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 59 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Ser Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 60 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 60 Gly Ser Gly Ala Gly Gly Ala Gly Gly Ala Tyr Gly Trp Gly Asp Asp 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 61 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 61 Gly Ser Gly Ala Gly Gly Arg Gly Gly Ala Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 62 27 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 62 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 63 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 63 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 64 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 64 Ser Gly Ala Gly Gly Ser Gly Gly Ser Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 65 37 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 65 Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Gly Tyr Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala Ala Ala 35 66 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 66 Gly Ser Gly Gly Gly Val Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 67 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 67 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 68 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 68 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 69 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 69 Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 70 37 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 70 Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Asp 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala Ala Ala 35 71 37 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 71 Gly Ser Gly Ala Gly Gly Arg Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala Ala Ala 35 72 30 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 72 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 73 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 73 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 74 32 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 74 Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Gly Tyr Gly 1 5 10 15 Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 75 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 75 Gly Ser Gly Ala Gly Gly Ala Gly Gly Tyr Gly Gly Tyr Gly Gly Tyr 1 5 10 15 Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 76 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 76 Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 77 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 77 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 78 23 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 78 Arg Arg Ala Gly His Glu Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala 20 79 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 79 Ser Gly Ala Gly Arg Ser Gly Gly Ser Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 80 31 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 80 Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Gly Tyr Gly 1 5 10 15 Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 81 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 81 Ser Gly Ala Gly Gly Ala Gly Gly Tyr Gly Gly Tyr Gly Gly Tyr Gly 1 5 10 15 Ser Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 82 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 82 Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 83 28 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 83 Gly Ser Gly Ala Gly Gly Arg Arg Gly Tyr Gly Ala Tyr Gly Ser Asp 1 5 10 15 Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 84 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 84 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 85 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 85 Gly Ser Gly Ala Gly Gly Ile Gly Gly Gly Phe Gly Arg Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 86 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 86 Arg Arg Ala Gly His Gly Arg Ser Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 87 27 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 87 Ser Ser Gly Ala Gly Gly Ser Gly Gly Ser Tyr Gly Trp Asp Tyr Glu 1 5 10 15 Ser Tyr Gly Ser Gly Ser Ala Ala Ala Ala Ala 20 25 88 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 88 Gly Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 89 25 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 89 Gly Ser Arg Arg Ser Gly His Asp Arg Ala Tyr Gly Ala Gly Ser Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 90 30 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 90 Gly Ser Ser Ala Arg Gly Gly Ser Gly Phe Tyr Glu Thr His Asp Ser 1 5 10 15 Tyr Ser Ser Tyr Gly Ser Gly Ser Ser Ser Ala Ala Ala Ala 20 25 30 91 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 91 Ser Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 92 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 92 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 93 37 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 93 Arg Arg Ala Gly His Asp His Ala Ala Gly Ser Ser Gly Gly Gly Tyr 1 5 10 15 Ser Trp Asp Tyr Ser Ser Tyr Gly Ser Glu Ser Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala Ala Ala 35 94 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 94 Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Gly Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 95 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 95 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 96 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 96 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 97 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 97 Gly Ser Gly Ala Gly Arg Ala Gly Gly Asp Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 98 32 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 98 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 99 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 99 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 100 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 100 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 101 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 101 Arg Gln Ala Gly His Glu Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 102 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 102 Ser Gly Ala Gly Gly Ser Gly Arg Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 103 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 103 Gly Ser Gly Ala Gly Gly Ala Gly Gly Asp Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 104 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 104 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 105 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 105 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 106 23 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 106 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala 20 107 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 107 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 108 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 108 Gly Ser Gly Ala Gly Gly Ala Gly Gly Asp Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 109 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 109 Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 110 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 110 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 111 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 111 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 112 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 112 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 113 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic

peptide 113 Gly Ser Gly Ala Gly Gly Ala Gly Gly Asp Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 114 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 114 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 115 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 115 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 116 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 116 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 117 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 117 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 118 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 118 Gly Ser Gly Ala Gly Gly Ala Gly Gly Asp Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 119 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 119 Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 120 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 120 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 121 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 121 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 122 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 122 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 123 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 123 Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 124 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 124 Ser Gly Ala Gly Gly Ala Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 125 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 125 Ser Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 126 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 126 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Asp Ser 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 127 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 127 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 128 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 128 Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 129 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 129 Ser Gly Ala Gly Gly Ala Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 130 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 130 Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 131 28 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 131 Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser Ser 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 132 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 132 Arg Arg Ala Gly Tyr Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 133 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 133 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 134 30 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 134 Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Gly Tyr Gly Ser Asp 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 135 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 135 Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 136 28 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 136 Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser Ser 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 137 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 137 Arg Arg Ala Gly Tyr Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 138 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 138 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 139 30 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 139 Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Gly Tyr Gly Ser Asp 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 140 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 140 Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 141 30 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 141 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 142 23 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 142 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala 20 143 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 143 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 144 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 144 Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 145 32 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 145 Ser Gly Ala Gly Gly Thr Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 146 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 146 Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 147 30 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 147 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 148 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 148 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 149 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 149 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asn Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 150 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 150 Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 151 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 151 Gly Ser Gly Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 152 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 152 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 153 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 153 Arg Arg Ala Gly His Asp Arg Ala Ala Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 154 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 154 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 155 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 155 Gly Ser Gly Ala Gly Gly Ala Gly Gly Asp Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 156 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 156 Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 157 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 157 Gly Ser Gly Ala Gly Gly Ala Gly Gly Asp Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 158 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 158 Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 159 36 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 159 Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala Ala 35 160 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 160 Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Arg Gly Asp Ser 1 5 10 15 Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 161 24 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 161 Arg Arg Ala Gly His Asp Arg Ser Ser Gly Ser Ala Ala Ala Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala Ala 20 162 33 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 162 Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Asp Tyr Gly Ser 1 5 10 15 Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala 163 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 163 Ser Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Asp Tyr Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 164 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 164 Gly Ser Gly Ala Gly Gly Ser Gly Gly Gly Tyr Gly Trp Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala 165 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 165 Gly Ser Gly Ala Gly Gly Arg Gly Asp Gly Gly Tyr Gly Ser Gly Ser 1 5 10 15 Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 166 37 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 166 Arg Arg Ala Gly His Asp His Ala Ala Gly Ser Ser Gly Gly Gly Tyr 1 5 10 15 Ser Trp Asp Tyr Ser Ser Tyr Gly Ser Glu Ser Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala Ala Ala 35 167 35 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 167 Gly Ser Gly Ala Gly Gly Val Gly Gly Gly Tyr Gly Gly Gly Asp Gly 1 5 10 15 Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 Ala Ala Ala 35 168 23 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 168 Ser Arg Arg Ala Gly His Asp Arg Ala Tyr Gly Ala Gly Ser Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Ala Ala 20 169 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 169

Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Arg 1 5 10 15 Gly Asp Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala 20 25 170 32 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 170 Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly Gly 1 5 10 15 Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala 20 25 30 171 23 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 171 Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly 1 5 10 15 Ser Asp Ser Ala Ala Ala Ala 20 172 32 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 172 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly 1 5 10 15 Gly Tyr Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala 20 25 30 173 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 173 Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Arg 1 5 10 15 Gly Asp Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala 20 25 174 32 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 174 Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly Gly 1 5 10 15 Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala 20 25 30 175 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 175 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly 1 5 10 15 Gly Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala 20 25 176 30 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 176 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ala 1 5 10 15 Gly Gly Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala 20 25 30 177 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 177 Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Arg Gly 1 5 10 15 Asp Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala Ala 20 25 178 34 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 178 Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ala Gly Gly Gly 1 5 10 15 Tyr Gly Trp Gly Asp Gly Gly Tyr Ser Ser Asp Ser Ala Ala Ala Ala 20 25 30 Ala Ala 179 23 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 179 Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Asp Gly Tyr Gly 1 5 10 15 Ser Asp Ser Ala Ala Ala Ala 20 180 23 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 180 Ala Gly Gly Arg Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly 1 5 10 15 Ser Asp Ser Ala Ala Ala Ala 20 181 28 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 181 Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Arg Gly 1 5 10 15 Asp Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala 20 25 182 31 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 182 Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly Ser Tyr 1 5 10 15 Ser Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala 20 25 30 183 29 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 183 Ala Ala Ala Ser Gly Ala Gly Gly Ser Gly Gly Tyr Gly Gly Tyr Gly 1 5 10 15 Gly Tyr Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala 20 25 184 23 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 184 Ala Gly Gly Val Gly Gly Gly Tyr Gly Trp Gly Asp Gly Gly Tyr Gly 1 5 10 15 Ser Asp Ser Ala Ala Ala Ala 20 185 28 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 185 Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Arg Gly 1 5 10 15 Asp Gly Gly Tyr Gly Ser Gly Ser Ser Ala Ala Ala 20 25 186 32 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 186 Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly Gly Ala Gly Gly Gly 1 5 10 15 Tyr Gly Trp Gly Asp Gly Gly Tyr Gly Ser Asp Ser Ala Ala Ala Ala 20 25 30 187 23 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide 187 Ala Gly Gly Ala Gly Gly Gly Tyr Gly Trp Gly Asp Asp Gly Tyr Gly 1 5 10 15 Ser Asp Ser Ala Ala Ala Ala 20

Claims

1-75. (canceled)

76. A surgically implantable device made at least partially of a biocompatible material comprising at least one protein selected from the group of proteins consisting of wild silkworm proteins or recombinant wild silkworm proteins or analogues thereof, in which the protein sequence of said at least one protein contains at least eight repeats of the triplet RGD.

77. A surgically implantable device according to claim 76 in which at least some of the at least eight repeats of the triplet RGD are located immediately adjacent to turns or predicted turns of a structure of the silkworm protein.

78. A surgically implantable device according to claim 76 in which said at least one protein is selected from the group of proteins consisting of Antheraea pernyii (TrEMBL O76786) or Antheraea yamamai (TrEMBL Q964F4) or Antheraea militta (Q81SB3).

79. A surgically implantable device according to claim 76, which is made of a plurality of elements of the biocompatible material.

80. A surgically implantable device according to claim 79 wherein the implant is substantially cylindrical and the elements of the biocompatible material are arranged longitudinally on a surface of the surgically implantable device.

81. A surgically implantable device according to claim 79 wherein the implant is substantially cylindrical and the elements of the biocompatible material are arranged in a helical manner on the surface of the implant.

82. A surgically implantable device according to claim 79 wherein the implant is substantially cylindrical and the elements of the biocompatible material are arranged circumferentially on the surface of the implant.

83. A surgically implantable device according to claim 76 of the preceding claims wherein the biocompatible material has been-mineralised.

84. A surgically implantable device according to claim 76 in which the biocompatible material consists of a composite material comprising one or more silk fibres, twisted threads, rods, sheets or tubes in a cross-linked protein matrix.

85. A surgically implantable device according to claim 84 in which said silk fibres, twisted threads, rods, sheets or tubes are woven, braided, embroidered or knitted together.

86. A surgically implantable device according to any of claim 76 being an endoluminal device.

87. A surgically implantable device according to any of claim 76 being a suture.

88. A surgically implantable device according to any of claim 76 being a stent device.

89. A surgically implantable device according to any of claim 76 being an anastomosis device.

90. A surgically implantable device according to any of claim 76 being a sleeve to guide regenerating nerve cell processes.

91. Method for the manufacture of an implant comprising:--a first step of applying elements of silk proteins to a former;--a second step of affixing the elements; and--a third step of removing the former.

92. The method of claim 91, wherein the second step of affixing the elements comprising applying protein material to the elements of silk proteins.

93. The method of claim 91, wherein the former has a substantially cylindrical shape with an outer surface and an inner surface, and the first step comprises applying longitudinal elements of silk proteins substantially lengthways along the outer surface of the former.

94. The method of claim 93, wherein the first step also comprises applying the longitudinal elements substantially lengthways along the inner surface of the former.

95. The method of any one of claims 91, further comprising a step of removing the former.

96. The method of any one of claims 91, further comprising a step of mineralisation.

97. The method of any one of claims 91, further comprising a step of abrading at least one surface of the implant so as to expose the elements of silk proteins.

Images