Heparin-binding peptides and uses thereof
Heparin-binding peptides are provided of the formula R 1 (X 1 B 1 B 2 X 2 B 3 X 3 Y 1 R 2 )R n R 3 , R 1 (X 1 B 1 B 2 B 3 X 2 X 3 B 4 X 4 Y 1 R 2 )R n R 3 , and C(X 1 B 1 B 2 B 3 X 2 X 3 B 4 X 4 ) n C; wherein X 1 , X 2 , X 3 , and X 4 are independently selected from the group consisting of hydropathic amino acids; B 1 , B 2 , B 3 , and B 4 are independently selected from the group consisting of basic amino acids; C is cysteine; Y 1 is zero or one to ten amino acid residues, wherein at least one amino acid residue is proline; n is an integer from one to ten; and R 1 , R 2 , and R 3 are independently selected segments containing from zero to twenty amino acid residues, provided, at least one of the segments R 1 , R 2 , and R 3 comprises at least one hydrophobic amino acid residue. The peptide C(X 1 B 1 B 2 B 3 X 2 X 3 B 4 X 4 ) n C is optionally cyclized via a disulfide bond formed between cysteine residues. The peptides are administered to reduce plasma LMWH and heparin levels and to reduce the anticoagulant effects of heparin and LMWH. The peptides are also administered to inhibit microbial growth and to inhibit mast cell serine proteases involved in various diseases and disorders. The peptides are also administered as carriers to deliver active agents.
1. A heparin-binding peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:5, SEQ ID NO:8 and SEQ ID NO:37,
wherein said heparin-binding peptide optionally comprises an amino-terminal protecting group or a carboxy-terminal protecting groups or both an amino-terminal protecting group and a carboxy-terminal protecting group.
2. A pharmaceutical composition comprising at least one peptide of claim 1 and a pharmaceutically-acceptable carrier.
3. A conjugate comprising a heparin-binding peptide according to claim 1 conjugated to at least one carrier molecule.
4. A conjugate according to claim 3 , wherein said carrier molecule is selected from the group consisting of collagen, hyaluronic acid and agarose.
5. A conjugate according to claim 3 , wherein said carrier molecule is further conjugated to a surgical sheet or mat.
6. The heparin binding peptide of claim 1 consisting of the amino acid sequence SEQ ID NO:1.
7. The heparin binding peptide of claim 1 consisting of the amino acid sequence SEQ ID NO:5.
8. The heparin binding peptide of claim 1 consisting of the amino acid sequence SEQ ID NO:8.
9. The heparin binding peptide of claim 1 consisting of the amino acid sequence SEQ ID NO:37.
10. The pharmaceutical composition according to claim 2 , wherein the heparin binding peptide consists of the amino acid sequence SEQ ID NO:1.
11. The pharmaceutical composition according to claim 2 , wherein the heparin binding peptide consists of the amino acid sequence SEQ ID NO:5.
12. The pharmaceutical composition according to claim 2 , wherein the heparin binding peptide consists of the amino acid sequence SEQ ID NO:8.
13. The pharmaceutical composition according to claim 2 , wherein the heparin binding peptide consists of the amino acid sequence SEQ ID NO:37.
14. The conjugate according to claim 3 , wherein the heparin binding peptide consists of the amino acid sequence SEQ ID NO:1.
15. The conjugate according to claim 3 , wherein the heparin binding peptide consists of the amino acid sequence SEQ ID NO:5.
16. The conjugate according to claim 3 , wherein the heparin binding peptide consists of the amino acid sequence SEQ ID NO:8.
17. The conjugate according to claim 3 , wherein the heparin binding peptide consists of the amino acid sequence SEQ ID NO:37.