Laminin a chain deduced amino acid sequence, expression vectors and active synthetic peptides

• US 5,211,657 A
• Filed: 11/07/1988
• Issued: 05/18/1993
• Est. Priority Date: 11/07/1988
• Status: Expired due to Term

• Current Assignee: United States Department Of Health And Human Services
• Original Assignee: United States Government As Represented By The Secretary of The Department of Health and Human Services
• Inventors: Sasaki, Makoto, Yamada, Yoshihiko, Kleinman, Hynda K., Martin, George R.
• Primary Examiner(s): Cannon, Alan W.
• Application Number:
  US07/267,564
• Time in Patent Office: 1,653 Days
• Field of Search: 514/2, 514/13-15, 530/322, 530/326, 530/327, 530/328, 530/331, 623/1, 623/11, 623/12, 623/66
• US Class Current: 623/1.48
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 31/047 Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
• CPC Class Codes: C07K 16/18 against material from animals or humans

Abstract

The present invention relates to peptides and derivatives thereof having laminin-like activity. The invention further relates to pharmaceutical compositions containing these peptides, to antibodies effective against these peptides, and to vectors containing a DNA sequence of cDNA coding for the A chain of laminin. The peptides of the invention may be used to treat diseases such as cancer.

Claims

1. Peptides and derivatives thereof having laminin A-like activity selected from the group consisting of:

(i) KCQAGTFALRGDNPQG,

(ii) CSKCQAGTFALR,

(iii) XFALRGDNPQG,

(iv) XSRARKQAASIKVAVSADR,

(v) XRKQAASIKVAVS,

(vi) XIKVAVSADR,

(vii) XSRNLSEIKLLISRARK

(viii) GLWNYIEREGKC,

(ix) KPLKTLEENLSRNLSEI,

(x ) DRLKPLKTLEENLSRNLSEI,

(xi) XGQIKKSPAVKVTHFKG,

(xii) XGQIKKSPAVKVT, and

(xiii) CIRAYQPQTSSTNYNTLTIL

wherein the X group is an amino acid which is not present in the A chain but is used in coupling the peptide to other materials.

2. The peptides of claim 1 wherein the peptides and derivatives thereof comprise protein polymers or cycled peptides.

3. A pharmaceutical composition comprising a therapeutically effective amount of a peptide of claim 1 and a pharmaceutically acceptable carrier therefor.

4. A pharmaceutical composition comprising 50 ng to 5 ug peptide per cm² of polymer surface of the polymer of claim 2.

5. A substrate active in promoting epithelial, endothelial or neural cell adhesion, migration, growth, collagenase IV production, neurite outgrowth, tumor formation and heparin binding, comprising the peptides of claim 1 and the expressed material from vectors containing a DNA sequence of cDNA coding for the A chain of laminin or a segment of DNA coding for a portion of the A chain, wherein the DNA sequence is in association with an expression regulatory sequence.

6. A method of stimulating cancer, which comprises administering to an animal a therapeutically effective amount of a peptide of claim 1.

7. The method of claim 6, wherein the animal is a mammal.

8. The method of claim 6, which comprises administering to the animal 0.01 gm to 0.1 gm/gm body weight of the peptide.

9. The method of claim 6, wherein the mode of administration is intravenous, intraperitoneally or via slow release pellet or pump.

10. A prosthetic device having a biologically active surface which exhibits cell attachment activity and growth activity, said surface having linked thereto a peptide of claim 1 or the expressed protein of a vector containing a DNA sequence of cDNA coding for the A chain of laminin or a segment of DNA coding for a portion of the A chain.

11. The prosthetic device of claim 10, wherein said surface comprises a portion of a vascular graft.

12. The prosthetic device of claim 10, wherein said surface comprises synthetic resin fiber.

13. The prosthetic device of claim 10, wherein said surface comprises a portion of a percutaneous device.

14. A method for promoting increased adhesion of epithelial or endothelial cells to vascular prostheses and other artificial organs comprising coating of the prostheses or organ with a protein selected from the group consisting of a peptide of claim 1 or expressed proteins of a vector containing a DNA sequence of cDNA coding for the A chain of laminin or a segment of DNA coding for a portion of the A chain.

15. An anti-adhesion factor for laminin-responsive cells comprising an antibody effective against a peptide of claim 1 or effective against an expressed protein of a vector containing a DNA sequence of cDNA coding for the A chain of laminin or a segment of DNA coding for a portion of the A chain.

16. A method for promoting the migration and growth of epithelial cells and nerves in a wound comprising administering to the wound a therapeutically effective amount of a protein selected from the group consisting of a peptide of claim 1 and the expressed protein of a vector containing a DNA sequence of cDNA coding for the A chain of laminin or a segment of DNA coding for a portion of the A chain.

17. A method for isolating a laminin cell surface receptor from detergent extracts of cells or cell membranes bound to a laminin affinity column, comprising adding to said cells or cell membranes a peptide of claim 1.