CA2301959A1 - Peptide having affinity for coagulation factor viii - Google Patents

Peptide having affinity for coagulation factor viii Download PDF

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Publication number
CA2301959A1
CA2301959A1 CA 2301959 CA2301959A CA2301959A1 CA 2301959 A1 CA2301959 A1 CA 2301959A1 CA 2301959 CA2301959 CA 2301959 CA 2301959 A CA2301959 A CA 2301959A CA 2301959 A1 CA2301959 A1 CA 2301959A1
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Canada
Prior art keywords
seq
peptide
type
strandedness
unknown
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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CA 2301959
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French (fr)
Inventor
Alois Jungbauer
Djuro Josic
Roman Necina
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Octapharma AG
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Octapharma AG
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Priority to CA 2301959 priority Critical patent/CA2301959A1/en
Publication of CA2301959A1 publication Critical patent/CA2301959A1/en
Abandoned legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/745—Blood coagulation or fibrinolysis factors
    • C07K14/755—Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/745—Assays involving non-enzymic blood coagulation factors
    • G01N2333/755—Factors VIII, e.g. factor VIII C [AHF], factor VIII Ag [VWF]

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Hematology (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Peptides Or Proteins (AREA)

Abstract

A peptide having the structure R1-X-R2, wherein R1 = NH2 or a peptide;
R2 = COOH or a peptide; and X = a peptide which is at least a tripeptide, preferably a hepta- to do-decapeptide, which undergoes affinity binding to factor VIII.

Description

SMB
Peptide Havinq~ Affinity for Coagulation Factor VIII
The present invention relates to a peptide having binding affinity for factor VIII, a support material to which the peptide according to the invention is bound, a diagnostic agent containing the peptide according to the invention, the use of the peptide for the labeling, identification or purification of factor VIII, . and a process for the preparation of the peptide according to the invention synthesized in a liquid or solid phase system.
A method perfectly Established in the prior art for the purification of, in particular, complex structures such as proteins is affinity chromatography (Yannis Chonis; ProcEas Affinity Chromatography, in: Separation Processes in Biotechnology, Ed. J.A. Asenjo, pages 401 to 494, Marcel Dekker, New York 1990; S.R. Narayanon, Preparative affinity chromatography of pro-teins, J. Chromatogr. A, 658 (1994), 237 to 258). In "Bioorganic & Medici-nal Chemistry", Vol. 4, No. 5, pp. 699 to 708, 1996, Huang, Ping Y. et al.
describe the use of peptides which can be employed for the affinity purifica-tion of von Willebrancl factor. Von Willebrand factor is a component of blood plasma and plays an important role in the stabilization of factor VIII.
Factor VIII itself is also a valuable plasma component which is of thera-peutical interest, in particular, namely for repairing disorders in the blood clotting cascade in which factor VIII plays an important role. In addition to factor VIII preparation by recombinant methods, preparation of factor VIII
from blood plasma still plays an important role.

_2_ A wide variety of methods for the preparation of factor VIII by chromato-graphic methods are known. This includes the use of immunoaffinity chromatographic methods wherein antibodies against factor VIII are immobilized on a support and samples containing factor VIII are contacted with this support material so that factor VIII can be isolated from the respective samples by immunoaffinity reactions.
However, in the latter method, there is a disadvantage, in particular, in that the antibodies are relatively large molecules which occupy a large portion of the surface of the support material and thus lead to a limitation of capacity.
Moreover, it is not trivial to bind the antibodies to the surface of this material and yet retaun and present the specific binding sites; thus, in the immobilization of antibodies, additional capacity is lost by inactivation of the affinity ligand. In addition, contaminations may occur by bleeding of the antibodies from the separation column.
It has been the object: of the present invention to provide a material which facilitates the purification of factor VIII.
According to the invention, this object is achieved by peptides having the features of claim 1.
The peptides according to the invention have the structure Rl-X-R2, wherein Rl is NHZ or a peptide, preferably containing not more than 20 amino acid units, R2 is COOH or a peptide, and X is a peptide which is at least a tripeptide, preferably a hepta- to dodecapeptide, which undergoes affinity binding to factor VIII.

Thus, in the structural element according to the invention, R1 represents the N-terminal end of a peptide represented by the structural element X, whereas RZ represents the carboxy terminal end of a peptide defined by X.
It will be understood by one skilled in the art that the structural elements include their respective salts and derivatives, such as N-modified deriva-tives or derivatives modified at the carboxy terminus.
Amino acids which can be employed for the preparation of the peptide according to the invention include both the naturally occurring amino acids and non-proteinogeniic amino acids. As a rule, they are a-amino acids.
Structural variants of the amino acids may be those which have modifica-tions in the side chain, cyclic peptides, branched or mixotropic peptides.
The structural element X comprises at least three amino acids which are connected by peptide bonds; preferably, the structural element X is a hepta-, octa- or nonapeptide, more preferably an octapeptide to decapep-tide, which is characterized by binding to factor VIII. Particularly preferred are the octapeptides explicitly stated in the sequence listing under the sequence identification numbers SEQ ID N0. 1 to SEQ ID NO. 94. The particularly preferred ~octapeptides having the stated structures according to SEQ ID NOS. 1 to 94 are capable of specifically binding to factor VIII.
According to the invention, those peptides are preferred which contain the structural element X :_ -R3-R4-RS-R6-R'-R8-R9-Ri°- wherein R3 = V or E, =M,WorY,RS=IorK,R6=KorS,R'=C,EorW,R8=EorF,R9=Yor E, Rl° = C or F, and Rl and R2 have the indicated meanings. The latter peptides will bind to human or recombinant factor VIII. Especially preferred are peptides in which R' = W, R8 = E, R9 = E or Y, Rl° = F or C, and Ri, R2 and R3 to R6 have i:he indicated meanings. This includes the peptides according to the invention having the SEQ ID NOS: 66, 72, 78, 84, 89 and 90. The latter peptides have a prominent affinity for both recombinant factor VIII and factor VIII prepared from plasma.
The octapeptides having the SEQ ID NOS. 61, 66, 71, 72, 76, 77, 78, 81 to 84, 89 and 90 are characterized by binding to pdFVIII (plasma-derived factor VIII). The peptide having the SEQ ID NO. 61 does not bind to recombinant factor VIII. The octapeptides having the SEQ ID NOS. 56 to 58, 66, 68, 71, 72, 76 to 78, 81 to 84 and 87 to 90 do bind to recombinant factor VIII; of these, the octapeptides having the SEQ ID NOS. 66, 71, 72, 76 to 78, 81 to 84, 89 and 90 also bind to plasma-derived factor VIII.
According to the invE~ntion, the octapeptides having the SEQ ID NOS. 66, 72, 78, 84, 89 and 90 are particularly preferred.
The peptides having the SEQ ID NOS. 66 and 90 to 94 are particularly suitable for the affinity chromatography of rFVIII (recombinant factor VIII), and the peptides 66, 72 and 91 to 94 are particularly suitable for the affinity chromatography of pdFVIII.
According to the invention, these peptides may also be used for the prepa-ration of a support material according to the invention. This support mate-rial has a surtace with peptides according to the invention bound thereto; it is the subject matter of claims 8 to 9.
The peptides according to the invention are bound to the surtace of the support material according to the invention, preferably by chemical bond-ing. "Chemical bonding" as used herein includes both covalent and ionic, hydrophobic and/or complex interactions.
The support material preferably consists of inorganic or organic, especially polymeric, material. llseful materials include the polymeric materiais which usually can be employed per se in the chromatography of biopolymers.

The peptides according to the invention are preferably bound to the surtace of the support maternal through spacers (arms). Such spacers are known to those skilled in the art. The spacers are preferably those which will not interfere with the afr~inity binding between factor VIII and the peptides in the chromatographic separation process.
Spacers usually consnsts of linear low-molecular weight hydrocarbon chains provided with functional groups at both ends. A summary of the state of the art is found in G.T. Hermanson, A.K. Mallia and P.K. Smith; Immobilized Affinity Ligand Techniques, Academic Press, Inc., San Diego, New York;
Boston, London, Sydney, Tokyo, Toronto, 1992. One end is bound to the solid support while the other end serves for binding the peptide ligand. The hydrocarbon chains may also be modified. In particular, useful spacers include diaminodipropylamine (DADPA) (3,3'-iminobis(propylamine)), succinic acid (as the anhydride), 6-aminocaproic acid, 1,3-diamino-2-propanol, 1,6-diaminohexane (DH) and/or ethylenediamine (EDA). Further, amino acids, peptides., sugars and other polyols may also serve as spacers.
Iminodiacetic acid or' lysine may also be used as spacers. For example, lysine is bound to a aupport as Fmoc-Lys(Fmoc)-OH or Fmoc-(Lys)-(Boc)-OH. Due to the introduction of the protective groups, lysine is bound to the support at the carboxy terminus. By selectively cleaving the protective groups, free amino acids are obtained to which at least one peptide can be bound. The amino groups of lysine may also be blocked by other protective groups.
As chromatographic supports, there may be used, in particular, polymers having a hydrophilic surface, e.g., so-called tentacle materials. It is also advantageous to imrnobilize the peptides according to the invention on compact porous disks and/or membranes, both preferably having a hydro-philic surface. Corresponding devices are described in WO-A-96/06158.

Due to the fact that the peptides according to the invention will interact with factor VIII, they peptide compounds according to the invention are suitable as diagnostic agents for factor VIII. Thus, the diagnostic agent according to the invention contains at least one peptide according to the invention or a support material according to the invention to which at least one peptide according to the invention is bound, and optionally auxiliary agents.
To recognize that a reaction has occurred between a peptide according to the invention and factor VIII, the peptide according to the invention is labeled. As the label, there may be used, for example, a radioactive label or a label using fluorescent ligands, the avidin/streptavidin system, or en-zymes which can cause color reactions, as generally known in the ELISA
technique.
The peptides according to the invention are suitable for the labeling, identii=ICation or purification of factor VIII.
The peptides according to the invention can be prepared by methods well established in the peptide chemistry, especially according to the Merrifield solid-phase synthesis or in liquid phase.
Examples Exams 1~ a 1 Affinity chromatography From membranes on which the respective peptides have been immobilized, 30 disks each having a diameter of 11 mm were punched out. They were packed in an HR 10 column (Pharmacia Biotechnology, Uppsala, Sweden) and fixed between two plugs.

_ 7 _ For all chromatographic experiments, the chromatographic system ProSys (Biosepra Inc., Marlborough, USA) was used. PBS buffer, pH 7.0, was used as an equilibration and washing buffer. For elution, 0.1 M glycine buffer, pH
3.0, was used. In all experiments, the flow rate was 0.1 ml/min.
pdFVIII
Lyophilized factor VIII from plasma was dissolved in 11 ml of distilled water to a concentration of 90 units/ml. Of this, 4 ml each was charged onto the column with a flow rate of 0.1 ml/min. Subsequently, the affinity supports were washed with PBS buffer, pH 7.0, until the UV signal (280 nm) again reached the baseline" The bound material was eluted with 0.1 M glycine, pH
3Ø The collected fractions were analyzed by SDS PAGE under reducing conditions and by WEatern blotting. Thus, peptides and the ~iAla-~iAla blank were examined for their capability of binding factor VIII from the Octavi preparation.
rFVIII
The binding of recombinant factor VIII was examined using Kogenate~
(Bayer, Germany). Four hundred microliters each of the preparation (200 units) was diluted with 1,400 NI of distilled water and then charged onto the affinity support with a flow rate of 0.1 ml/min: Washing was again per- .
formed with PBS, pH 7.0, and the following elution was performed with 0.1 M glycine, pH 3Ø The fractions were analyzed by SDS PAGE under reducing conditions and by Western blotting.
SDS PAGE
The percolate and the eluates of all runs were collected and analyzed by SDS PAGE under reducing conditions and by Western blotting.

_ 8 _ For the separation, 4 to 20% tris-glycine gels from Novex were used. SDS
sample buffer (1.5 M Tris-HCI, pH 8.45, 1.2 ml of glycerol, 0.4 g of SDS, 0.1% Coomassie blue, 0.1% phenol red per 10 ml) and 5% (3-mercapto-ethanol were added to the samples, followed by incubation over night at 4 °C. After the separation, the gels were subjected to silver staining and recorded by scanning.
Western Blot After completion of the electrophoretic separation, the gels were electro-blotted to a nitrocellulose membrane at a constant current of 200 mA for two hours. Then, the membrane was blocked with PBS + 3% BSA for two hours. After washing with PBS buffer, addition of the anti-FVIII antibody mixture (Chemicon International Inc., MAB038, Sera-Lab MAS 530, MAS
531, MAS 532) was performed for two hours. After washing with PBS, incubation with anti-mouse IgG/alkaline phosphatase conjugate (1:1000;
Sigma Chemicals, A-3438) was pertormed for one hour. The blot was developed with 0.1 M tris, pH 9.2, NBT and BCIP.
The peptides SEQ ID~ NOS. 55 to 90 were immobilized on a membrane.
After equilibration with PBS buffer, pH 7.0, one membrane was incubated with factor VIII Octavi~ (240 units in 10 ml PBS, pH 7.0, with 1% BSA), another membrane was incubated with Kogenate~ (250 units in 10 ml of PBS, pH 7.0, with 1°io BSA), and one membrane was incubated only with PBS, pH 7.0, with 1% BSA, for two hours. The membranes occupied by the peptides were carefully washed with PBS buffer, pH 7.0, and subsequently contacted with the anti-FVIII antibodies (Chemicon International Inca, MAB038, Sera-Lab MAS 530, MAS 531, MAS 532) for one hour. After washing and incubation with anti-mouse-IgG/alkaline phosphatase conju-gate (1:1000, Sigma Chemicals, A-4338), the membranes were developed using NBT and BCIP iin 0.1 M tris buffer, pH 9.2. Factor VIII binding pep-_g_ tides appeared as colored spots. The control membrane (only with PBS, pH
7.0, without factor VI:fI) was compared with the two other membranes.
ExamJ~le 2 Affinity chromatography with the peptides The affinity chromatography was performed as described in Example 1.
Affinity chromatography with pdFVIII
When the (~3Ala)Z coni:rol membrane is used, only a very small elution peak can be detected (see Figure 1). Also in the silver staining of the SDS PAGE
under reducing conditions, only rather weakly colored bands appear. The Western blot of the eluate is slightly positive.
The peptides SEQ ID NOS. 66 (VMKSWEEF) and 72 (EWIKWEEF) (Figure 2) exhibit larger elution peaks and more intensely colored bands in the SDS
PAGE under reducing conditions (see Figure 3) and silver staining. In both cases, the Western blot is positive.
Binding of recombinant factor VIII from Kogenate~ from Bayer As can be seen from the chromatogram (Figure 4), the control membrane with immobilized ~iAla-~iAla binds recombinant factor VIII but very slightly.
The Western blot of the eluate was positive.
The elution peaks from the peptides VMKSWEEF (SEQ ID NO: 66), EYKSWEEF (peptide 90) in Figure 4 are clearly larger than that of the ~Ala-~iAla control membrane. In both cases, the Western blot of the eluates is positive (Figure 4).

SEQUENCE LISTING
(1) GENERAL INFORMATION:
(i) APPLICANT:
(A) NAME: Octapharma AG
(B) STREET: Seidenstrasse 2 / Postfach (C) CITY: Lachen (E) COUNTRY: Switzerland (F) POSTAL CODE (ZIP): CH-8853 (ii) TITTLE OF INVENTION: Peptide having affinity for coagulation factor VIII
(iii) NUMBER OF SEQUENCES: 94 (iv) CORRESPONDENCE ADDRESS:
(A) ADDRESSEE: Swabey Ogilvy Renault (B) STREET: 1981 McGill College, Suite 1600 (C) CITY: Montreal (D) STATE: Quebec (E) COUNTRY: Canada (F) ZIP: H3A 2Y3 (v) COMPUTER READABLE FORM:
(A) MEDIUM TYPE: Floppy disk (B) COMPUTER: IBM PC compatible (C) OPERATING SYSTEM: PC-DOS/MS-DOS
(D) SOFTWARE: PatentIn Release #1.0, Version #1.30 (EPO) (vi) CURRENT APPLICATION DATA:
(A) APPLICATION NUMBER: 2,301,959 (B) FILING DATE: 22-MAR-2000 (C) CLASSIFICATION:
(viii) ATTORNEY/AGENT INFORMATION:
(A) NAME: Kevin P. Murphy (B) REGISTRATION NUMBER: 3302 (C) REFERENCE/DOCKET NUMBER: 6603-144 KPM/ld (ix) TELECOMMUNICATION INFORMATION:
(A) TELEPHONE: 514-845-7126 (B) TELEFAX: 514-288-8389 (C) TELEX:
(2) INFORMATION FOR SEQ ID N0: 1:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 1:
Gly Cys Val Ser Gly Cys Leu Cys (2) INFORMATION FOR SEQ ID NO: 2:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 2:
Cys Val Ser Gly Cys Leu Cys Pro (2) INFORMATION FOR SEQ ID N0: 3:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: S Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 3:
Val Ser Gly Cys Leu Cys Pro Pro (2) INFORMATION FOR SEQ ID N0: 4:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOG't: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 4:
Ser Gly Cys Leu Cys Pro Pro Gly (2) INFORMATION FOR SEQ ID N0: 5:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 5:
Gly Cys Leu Cys Pro Pro Gly Met (2) INFORMATION FOR SEQ ID NO: 6:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 6:
Cys Leu Cys Pro Pro Gly Met Val (2) INFORMATION FOR SEQ ID NO: 7:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 7:
Leu Cys Pro Pro Gly Met Val Arg (2) INFORMATION FOR SEQ ID NO: 8:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 8:
Cys Pro Pro Gly Met Val Arg His (2) INFORMATION FOR SEQ ID N0: 9:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 9:
Pro Pro Gly Met Val Arg His Glu (2) INFORMATION FOR SEQ ID N0: 10:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 10:
Pro Gly Met Val Arg His Glu Asn (2) INFORMATION FOR SEQ ID N0: 11:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 11:
Gly Met Val Arg His Glu Asn Arg (2) INFORMATION FOR SEQ ID N0: 12:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Arnino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 12:
Met Val Arg His Glu Asn Arg Cys (2) INFORMATION FOR SEQ ID NO: 13:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 13:
Val Arg His Glu Asn Arg Cys Val (2) INFORMATION FOR SEQ ID NO: 14:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 14:
Arg His Glu Asn Arg Cys Val Ala (2) INFORMATION FOR SEQ ID NO: 15:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 15:
His Glu Asn Arg Cys Val Ala Leu (2) INFORMATION FOR SEQ ID N0: 16:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: S Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 16:
Glu Asn Arg Cys Val Ala Leu Glu (2) INFORMATION FOR SEQ ID N0: 17:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 17:
Asn Arg Cys Val Ala Leu Glu Arg (2) INFORMATION FOR SEQ ID NO: 18:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 18:
Arg Cys Val Ala Leu Glu Arg Cys (2) INFORMATION FOR SEQ ID NO: 19:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 19:
Cys Val Ala Leu Glu Arg Cys Pro (2) INFORMATION FOR SEQ ID NO: 20:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Atnino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 20:
Val Ala Leu Glu Arg Cys Pro Cys (2) INFORMATION FOR SEQ ID NO: 21:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 21:
Ala Leu Glu Arg Cys Pro Cys Phe (2) INFORMATION FOR SEQ ID NO: 22:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 22:
Leu Glu Arg Cys Pro Cys Phe His (2) INFORMATION FOR SEQ ID NO: 23:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 23:
Glu Arg Cys Pro Cys Phe His Gln (2) INFORMATION FOR SEQ ID NO: 24:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 24:
Arg Cys Pro Cys Phe His Gln Gly (2) INFORMATION FOR SEQ ID NO: 25:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 25:
Cys Pro Cys Phe His Gln Gly Lys (2) INFORMATION FOR SEQ ID N0: 26:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 26:
Pro Cys Phe His Gln Gly Lys Glu (2) INFORMATION FOR SEQ ID NO: 27:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 27:
Cys Phe His Gln Gly Lys Glu Tyr Z J
(2) INFORMATION FOR SEQ ID NO: 28:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 28:
Phe His Gln Gly Lys Glu Tyr Ala (2) INFORMATION FOR SEQ ID NO: 29:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 29:
His Gln Gly Lys Glu Tyr Ala Pro (2) INFORMATION FOR SEQ ID N0: 30:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 30:
Gln Gly Lys Glu Tyr Ala Pro Gly (2) INFORMATION FOR SEQ ID NO: 31:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: S Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIP~PION: SEQ ID NO: 31:
Gly Lys Glu Tyr Ala Pro Gly Glu (2) INFORMATION FOR SEQ ID N0: 32:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 32:
Lys Glu Tyr Ala Pro Gly Glu Thr (2) INFORMATION FOR SEQ ID NO: 33:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 33:
Glu Tyr Ala Pro Gly Glu Thr Val (2) INFORMATION FOR SEQ ID N0: 34:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 34:
Tyr Ala Pro Gly Glu Thr Val Lys (2) INFORMATION FOR SEQ ID N0: 35:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 35:
Ala Pro Gly Glu Thr Val Lys Ile (2) INFORMATION FOR SEQ ID NO: 36:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 36:
Pro Gly Glu Thr Val Lys Ile Gly (2) INFORMATION FOR SEQ ID N0: 37:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 37:
Gly Glu Thr Val Lys Ile Gly Cys (2) INFORMATION FOR SEQ ID N0: 38:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 38:
Glu Thr Val Lys Ile Gly Cys Asn (2) INFORMATION FOR SEQ ID N0: 39:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 39:
Thr Val Lys Ile Gly Cys Asn Thr (2) INFORMATION FOR SEQ ID N0: 40:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 40:
Val Lys Ile Gly Cys Asn Thr Cys (2) INFORMATION FOR SEQ ID N0: 41:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 41:
Lys Ile Gly Cys Asn Thr Cys Val (2) INFORMATION FOR SEQ ID N0: 42:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 42:
Ile Gly Cys Asn Thr Cys Val Cys (2) INFORMATION FOR SEQ ID NO: 43:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 43:
Gly Cys Asn Thr Cys Val Cys Arg (2) INFORMATION FOR SEQ ID NO: 44:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 44:
Cys Asn Thr Cys Val Cys Arg Asp (2) INFORMATION FOR SEQ ID N0: 45:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 45:
Asn Thr Cys Val Cys Arg Asp Arg (2) INFORMATION FOR SEQ ID NO: 46:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 46:
Thr Cys Val Cys Arg Asp Arg Lys (2) INFORMATION FOR SEQ ID N0: 47:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 47:
Cys Val Cys Arg Asp Arg Lys Trp (2) INFORMATION FOR SEQ ID NO: 48:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 48:
Val Cys Arg Asp Arg Lys Trp Asn (2) INFORMATION FOR SEQ ID NO: 49:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 49:
Cys Arg Asp Arg Lys Trp Asn Cys (2) INFORMATION FOR SEQ ID N0: 50:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 50:
Arg Asp Arg Lys Trp Asn Cys Thr (2) INFORMATION FOR SEQ ID N0: 51:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 51:
Asp Arg Lys Trp Asn Cys Thr Asp (2) INFORMATION FOR SEQ ID N0: 52:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 52:
Arg Lys Trp Asn Cys Thr Asp His (2) INFORMATION FOR SEQ ID NO: 53:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 53:
Lys Trp Asn Cys Thr Asp His Val (2) INFORMATION FOR SEQ ID NO: 54:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 54:
Trp Asn Cys Thr Asp His Val Cys (2) INFORMATION FOR SEQ ID N0: 55:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 55:
Val Met Ile Lys Cys Glu Tyr Cys (2) INFORMATION FOR SEQ ID N0: 56:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 56:
Val Met Ile Lys Cys Glu Glu Phe (2) INFORMATION FOR SEQ ID N0: 57:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 57:
Val Met Ile Lys Glu Phe Tyr Cys (2) INFORMATION FOR SEQ ID NO: 58:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 58:
Val Met Ile Lys Glu Phe Glu Phe (2) INFORMATION FOR SEQ ID N0: 59:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 59:
Val Met Ile Lys Trp Glu Tyr Cys (2) INFORMATION FOR SEQ ID N0: 60:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 60:
Val Met Ile Lys Trp Glu Glu Phe (2) INFORMATION FOR SEQ ID NO: 61:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 61:
Val Met Lys Ser Cys Glu Tyr Cys (2) INFORMATION FOR SEQ ID N0: 62:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 62:
Val Met Lys Ser Cys Glu Glu Phe (2) INFORMATION FOR SEQ ID NO: 63:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 63:
Val Met Lys Ser Glu Phe Tyr Cys (2) INFORMATION FOR SEQ ID NO: 64:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 64:
Val Met Lys Ser Glu Phe Glu Phe (2) INFORMATION FOR SEQ ID N0: 65:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 65:
Val Met Lys Ser Trp Glu Tyr Cys (2) INFORMATION FOR SEQ ID NO: 66:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 66:
Val Met Lys Ser Trp Glu Glu Phe (2) INFORMATION FOR SEQ ID N0: 67:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 67:
Glu Trp Ile Lys Cys Glu Tyr Cys (2) INFORMATION FOR SEQ ID NO: 68:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 68:
Glu Trp Ile Lys Cys Glu Glu Phe (2) INFORMATION FOR SEQ ID NO: 69:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 69:
Glu Trp Ile Lys Glu Phe Tyr Cys (2) INFORMATION FOR SEQ ID NO: 70:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 70:
Glu Trp Ile Lys Glu Phe Glu Phe (2) INFORMATION FOR SEQ ID NO: 71:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOG'~: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 71:
Glu Trp Ile Lys Trp Glu Tyr Cys (2) INFORMATION FOR SEQ ID N0: 72:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 72:
Glu Trp Ile Lys Trp Glu Glu Phe (2) INFORMATION FOR SEQ ID NO: 73:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 73:
Glu Trp Lys Ser Cys Glu Tyr Cys (2) INFORMATION FOR SEQ ID NO: 74:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 74:
Glu Trp Lys Ser Cys Glu Glu Phe (2) INFORMATION FOR SEQ ID NO: 75:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 75:
Glu Trp Lys Ser Glu Phe Tyr Cys (2) INFORMATION FOR SEQ ID NO: 76:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 76:
Glu Trp Lys Ser Glu Phe Glu Phe (2) INFORMATION FOR SEQ ID N0: 77:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 77:
Glu Trp Lys Ser Trp Glu Tyr Cys (2) INFORMATION FOR SEQ ID N0: 78:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 78:
Glu Trp Lys Ser Trp Glu Glu Phe (2) INFORMATION FOR SEQ ID NO: 79:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 79:
Glu Tyr Ile Lys Cys Glu Tyr Cys (2) INFORMATION FOR SEQ ID N0: 80:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 80:
Glu Tyr Ile Lys Cys Glu Glu Phe (2) INFORMATION FOR SEQ ID N0: 81:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 81:
Glu Tyr Ile Lys Glu Phe Tyr Cys (2) INFORMATION FOR SEQ ID NO: 82:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 82:
Glu Tyr Ile Lys Glu Phe Glu Phe (2) INFORMATION FOR SEQ ID NO: 83:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 83:
Glu Tyr Ile Lys Trp Glu Tyr Cys (2) INFORMATION FOR SEQ ID NO: 84:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 84:
Glu Tyr Ile Lys Trp Glu Glu Phe (2) INFORMATION FOR SEQ ID N0: 85:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 85:
Glu Tyr Lys Ser Cys Glu Tyr Cys (2) INFORMATION FOR SEQ ID N0: 86:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 86:
Glu Tyr Lys Ser Cys Glu Glu Phe (2) INFORMATION FOR SEQ ID NO: 87:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 87:
Glu Tyr Lys Ser Glu Phe Tyr Cys (2) INFORMATION FOR SEQ ID NO: 88:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 88:
Glu Tyr Lys Ser Glu Phe Glu Phe (2) INFORMATION FOR SEQ ID N0: 89:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 89:
Glu Tyr Lys Ser Trp Glu Tyr Cys (2) INFORMATION FOR SEQ ID NO: 90:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 90:
Glu Tyr Lys Ser Trp Glu Glu Phe (2) INFORMATION FOR SEQ ID NO: 91:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 10 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 91:
Leu Cys Pro Pro Gly Met Val Arg His Glu (2) INFORMATION FOR SEQ ID NO: 92:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 9 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 92:
Arg Cys Pro Cys Phe His Gln Gly Lys (2) INFORMATION FOR SEQ ID N0: 93:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 9 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 93:
Cys Phe His Gln Gly Lys Glu Tyr Ala (2) INFORMATION FOR SEQ ID NO: 94:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 12 Amino acids (B) TYPE: Amino acid (C) STRANDEDNESS: Single strand (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: Peptide (xi) SEQUENCE DESCRIPTION: SEQ ID N0: 94:
Arg Asp Arg Lys Trp Asn Cys Thr Asp His Val Cys

Claims (13)

1. A peptide having the structure R1-X-R2, wherein R1 = NH2 or a peptide;
R2 = COOH or a peptide; and X = a peptide which is at least a tripeptide, preferably a hepta- to dodecapeptide, which undergoes affinity binding to factor VIII.
2. The peptide according to claim 1, characterized in that X is an octapeptide to dodecapeptide.
3. The peptide according to claim 1, wherein X = -R3-R4-R5-R6-R7-R8-R9-R10.

R3 = V or E;
R4 = M, W or R5 = I or K;
R6 = K or S;
R7 = C, E or W;
R8 = E or F;
R9 = Y or E;
R10 = C or F; and R1 and R2 have the indicated meanings.
4. The peptide according to claim 2, characterized in that X is selected from the group of octapeptides consisting of the sequences having the SEQ ID NOS. 1 to 94.
5. The peptide according to claim 3, wherein R7 = W:
R8 = E;
R9 = E or Y;
R10 = F or C; and R1, R2 and R3 to R6 have the indicated meanings.
6. The peptide according to claim 3 having the amino acid sequence according to SEQ ID NOS. 55 to 90.
7. The peptide according to claim 1 and/or 2 having the SEQ ID NOS. 91 to 94.
8. A support material having a surface to which peptides according to at least one of claims 1 to 7 are bound.
9. The support material according to claim 8 consisting of inorganic or organic, especially polymeric, material.
10. The support material according to claim 8 and/or 9, wherein said peptide or peptides are bound to the surface of the support material through spacers.
11. A diagnostic agent containing at least one peptide according to at least one of claims 1 and/or 7, a support material according to at least one of claims 8 to 10, and optionally auxiliary agents, and op-tionally at least one peptide in a labeled form.
12. Use of the peptides according to at least one of claims 1 to 7 for the labeling, identification or purification of factor VIII.
13. A process for the preparation of the peptides according to at least one of claims 1 to 7 by liquid or solid phase synthesis.
CA 2301959 2000-03-22 2000-03-22 Peptide having affinity for coagulation factor viii Abandoned CA2301959A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA 2301959 CA2301959A1 (en) 2000-03-22 2000-03-22 Peptide having affinity for coagulation factor viii

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CA 2301959 CA2301959A1 (en) 2000-03-22 2000-03-22 Peptide having affinity for coagulation factor viii

Publications (1)

Publication Number Publication Date
CA2301959A1 true CA2301959A1 (en) 2001-09-22

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CA 2301959 Abandoned CA2301959A1 (en) 2000-03-22 2000-03-22 Peptide having affinity for coagulation factor viii

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011131510A2 (en) 2010-04-21 2011-10-27 Novo Nordisk A/S Selective modification of proteins
CN106046148A (en) * 2016-06-27 2016-10-26 新乡医学院 Method for implementing affinity purification on coagulation factor VIII by using peptide ligand

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011131510A2 (en) 2010-04-21 2011-10-27 Novo Nordisk A/S Selective modification of proteins
CN106046148A (en) * 2016-06-27 2016-10-26 新乡医学院 Method for implementing affinity purification on coagulation factor VIII by using peptide ligand

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