Angiogenic heparin-binding epitopes, peptide amphiphiles, self-assembled compositions and related methods of use

• US 20070277250A1
• Filed: 03/06/2006
• Published: 11/29/2007
• Est. Priority Date: 03/04/2005
• Status: Active Grant

• Current Assignee: Northwestern University
• Original Assignee: Northwestern University
• Inventors: Stupp, Samuel, Rajangam, Kanya, Hulvat, James
• Granted Patent: US 7,851,445 B2
• Time in Patent Office: Days
• US Class Current: 800/9
• CPC Class Codes: A61K 38/04 Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof enzyme inhibitors A61K38/005; gastrins A61K38/2207, somatostatins A61K38/31, melanotropins A61K38/34 ; protease inhibitors A61K38/55
• CPC Class Codes: A61K 47/542 Carboxylic acids, e.g. a fatty acid or an amino acid
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Peptide amphiphiles and related compositions comprising sulfated polysaccharides, such as but not limited to sulfated glycosaminoglycans, and methods of use relating to the encapsulation and/or controlled release of angiogenic growth factor(s).

Claims

1. An amphiphilic peptide compound comprising a hydrophobic component and a peptide component, said hydrophobic component coupled to said peptide component at one of the C-terminus and the N-terminus thereof, said peptide component comprising residues capable of non-covalent interaction with a sulfated polysaccharide.

2. The compound of claim 1 wherein said peptide component comprises residues interactive with a sulfated glycosaminoglycan selected from heparin sulfate, heparan sulfate and combinations thereof.

3. The compound of claim 1 wherein said hydrophobic component comprises an alkyl moiety ranging from about C6 to about C22.

4. The compound of claim 1 wherein said interactive residues comprise at least one hydrophobic residue (X) selected from alanine, glycine, leucine, isoleucine, phenylalanine, proline, valine and combinations thereof, and at least one basic residue (B) selected from arginine, histidine and lysine.

5. The compound of claim 4 wherein said interactive residues comprise a sequence selected from XBBBXXBX, XXXXBBBB, XXXXBBB, XXXXBB, and XXXXB, wherein X and B are each independently selected from said hydrophobic residues and said basic residues.

6. The compound of claim 5 wherein said interactive residues comprise a sequence selected from SEQ ID NO:

1 LRKKLGKA and SEQ ID NO;

2 LLGARKKK.

7. The compound of claim 5 wherein said peptide component comprises a moiety selected from a C-terminus amide, a bioactive epitope sequence and combinations thereof.

8. The compound of claim 6 in composition with a sulfated polysaccharide, said composition comprising a micellar configuration.

9. The compound of claim 8, said composition wherein said polysaccharide is a sulfated glycosaminoglycan selected from heparin sulfate, heparan sulfate and combinations thereof.

10. The compound of claim 9, said compositions interactive with an angiogenic growth factor.

11. The compound of claim 10, said growth factor selected from a heparin binding growth factor, a heparan binding growth factor and combinations thereof.

27. A method of inducing angiogenesis, said method comprising:

providing an amphiphilic peptide compound of claim 1;

incorporating a sulfated polysaccharide with said peptide compound; and

contacting said composition with a cellular medium and an angiogenic growth factor, said contact with said medium for a time and in an amount of at least one of said composition and said growth factor at least partially sufficient for angiogenesis.

28. The method of claim 27 wherein said interactive residues comprise a sequence selected from XBBBXXBX, XXXXBBBB, XXXXBBB, XXXXBB, and XXXXB, wherein X is independently selected from alanine, glycine, leucine, isoleucine, phenylalanine, proline and valine, and B is independently selected from arginine, histidine and lysine;

and said polysaccharide is a sulfated glycosaminoglycan selected from heparin sulfate, heparan sulfate and combinations thereof.

29. The method of claim 28 wherein said growth factor is exogenous to said medium.

30. The method of claim 28 contacting said peptide compound and said medium, prior to incorporation of said glycosaminoglycan.

31. The method of claim 30 wherein said contact is in vivo.

32. The method of claim 31 contacting mammalian ischemic tissue.

12. A composition comprising a sulfated polysaccharide and an amphiphilic peptide comprising a hydrophobic component and a peptide component, said hydrophobic component coupled to said peptide component at one of the C-terminus and the N-terminus thereof, said peptide component comprising residues capable of non-covalent interaction with said polysaccharide, said composition comprising a micellar configuration.

13. The composition of claim 12 wherein said polysaccharide is a sulfated glycosaminoglycan selected from heparin sulfate, heparan sulfate and combinations thereof.

14. The composition of claim 12 wherein said interactive residues comprise a sequence selected from XBBBXXBX, XXXXBBBB, XXXXBBB, XXXXBB, and XXXXB, wherein X is independently selected from alanine, glycine, leucine, isoleucine, phenylalanine, proline and valine, and B is independently selected from arginine, histidine and lysine.

15. The composition of claim 14 comprising an angiogenic growth factor selected from a heparin binding growth factor, a heparan binding growth factor and combinations thereof.

16. The composition of claim 15 wherein said factor is selected from VEGF and FGF-2.

17. The composition of claim 16 in contact with endothelial cells.

18. The composition of claim 17 wherein said interactive residues comprise a sequence selected from SEQ ID NO:

1 LRKKLGKA and SEQ ID NO;

2 LLGARKKK.

19. The composition of claim 14 in contact with a mammalian ischemic skin wound.

20. The composition of claim 19 wherein said interactive residues comprise a sequence selected from SEQ ID NO:

1 LRKKLGKA and SEQ ID NO;

2 LLGARKKK.

21. A method of using an amphiphilic peptide composition to activate an angiogenic growth factor, said method comprising:

providing an amphiphilic peptide compound comprising a hydrophobic component and a peptide component, said hydrophobic component coupled to said peptide component at one of the C-terminus and the N-terminus thereof, said peptide component comprising residues capable of non-covalent interaction with a sulfated glycosaminoglycan;

incorporating a sulfated glycosaminoglycan with said peptide compound, said glycosaminoglycan selected from heparin sulfate, heparan sulfate and combinations thereof; and

interacting said peptide composition with an angiogenic growth factor.

22. The method of claim 21 wherein said interactive residues comprise a sequence selected from XBBBXXBX, XXXXBBBB, XXXXBBB, XXXXBB, and XXXXB, wherein X is independently selected from alanine, glycine, leucine, isoleucine, phenylalanine, proline and valine, and B is independently selected from arginine, histidine and lysine.

23. The method of claim 22 wherein said interaction is in vivo.

24. The method of claim 23 wherein said interaction is substantially absent exogenous growth factor.

25. The method of claim 24 wherein said interactive residues comprise a sequence selected from SEQ ID NO:

1 LRKKLGKA and SEQ ID NO;

2 LLGARKKK.

26. The method of claim 23 contacting mammalian ischemic tissue.