Chemotactic wound healing peptides

• US 5,436,228 A
• Filed: 09/28/1993
• Issued: 07/25/1995
• Est. Priority Date: 12/12/1990
• Status: Expired due to Term

• Current Assignee: Research Corporation
• Original Assignee: Andrew Kang, Arnold E. Postlethwaite, Jerome Seyer
• Inventors: Postlethwaite, Arnold E., Kang, Andrew, Seyer, Jerome
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): HUFF, SHEELA JITENDRA
• Application Number:
  US08/127,909
• Time in Patent Office: 665 Days
• Field of Search: 514/12-14, 514/16, 530/324, 530/326, 530/329
• US Class Current: 514/8.9
• 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: C07K 14/495 Transforming growth factor [TGF]

Abstract

Peptides corresponding to an no acid sequences in the C-terminal region of TGF-β are provided. The peptides all contain at least a seven amino acid sequence substantially corresponding to the amino acid sequence of TGF-β1 amino acids 368-374: VYYVGRK, as well as homologs and analogs thereof. The peptides have chemotactic activity towards fibroblasts, monocytes and neutrophils and induce fibroblast proliferation and collagen synthesis. The peptides may be used in compositions and methods for promoting wound healing.

Claims

1. A chemotactic peptide having an amino acid sequence as set forth in SEQ ID NO. 1, or a homolog, or an analog thereof.

6. A method for inducing either in vitro or in vivo chemotaxis of fibroblasts and/or inflammatory cells comprising administering to the fibroblasts and/or inflammatory cells at least one peptide of any one of claims 1-5 in an amount effective to induce chemotaxis.

7. A method for inducing or a homolog thereof and a pharmaceutically acceptable carrier proliferation of fibroblasts and/or inflammatory cells comprising administering to the fibroblasts and/or inflammatory cells at least one peptide of any one of claims 1-5 in an amount effective to induce cellular proliferation.

8. A method for inducing either in vitro or in vivo collagen synthesis by fibroblasts comprising administering to the fibroblasts at least one peptide of any one of claims 1-5 in an amount effective to induce collagen synthesis.

9. A method for promoting wound healing in a patient comprising administering to the patient at least one peptide of any one of claims 1-5 in an amount effective to promote wound healing in the patient.

13. An analog of a chemotactic peptide set forth in any one of claims 1-5 having a cysteine residue attached to the C-terminal or N-terminal end of said peptide.

2. A chemotactic peptide wherein the amino acid sequence of the peptide is selected from the group consisting of SEQ ID NO. 1, SEQ. ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5 and analogs thereof.

3. A chemotactic peptide wherein the amino acid sequence of the peptide is selected from the group consisting of SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9, SEQ ID NO. 10 and analogs thereof.

4. A chemotactic peptide wherein the amino acid sequence of the peptide is selected from the group consisting of SEQ ID NO. 11, SEQ ID NO. 12, SEQ ID NO. 13, SEQ ID NO. 14, SEQ ID NO. 15 and analogs thereof.

5. A chemotactic peptide wherein the amino acid sequence of the peptide is selected from the group consisting of SEQ ID NO. 16, SEQ ID NO. 17, SEQ ID NO. 18, SEQ ID NO. 19, SEQ ID NO. 20 and analogs.

10. A chemotactic peptide consisting of a seven amino acid sequence as set forth in SEQ ID NO. 1.

11. A chemotactic peptide having an amino acid sequence selected from the group consisting of SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4 and SEQ ID NO. 5.

12. An analog of a chemotactic peptide set forth in SEQ ID NO. 6 having a cysteine residue attached to the C-terminal end of said peptide.

14. A pharmaceutical composition comprising either a peptide of SEQ ID NO. 1.