HEPARIN-PEPTIDE BIOCONJUGATES AND USES THEREOF

1 . A synthetic bioconjugate comprising a derivatized heparin conjugated to from one to about 10 peptide(s) comprising an amino acid sequence GELYKSILY (SEQ ID NO: 2), wherein the peptide(s) are bound to the heparin via a hydrazide-carbonyl linkage, and wherein the heparin is derivatized by reacting with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), and the derivatized heparin does not contain oxidatively cleaved saccharide units.

2 . The synthetic bioconjugate of claim 1 , wherein the heparin comprises from about 1 to about 75 percent (%) functionalization, wherein the percent (%) functionalization is determined by a percent of disaccharide units on the heparin which are functionalized with peptide.

3 . The synthetic bioconjugate of claim 2 , wherein the heparin comprises from about 5 to about 30 percent (%) functionalization, or from about 10 to about 40 percent (%) functionalization.

4 . The synthetic bioconjugate of claim 2 , wherein the heparin comprises about 25 percent (%) functionalization, or about 30 percent (%) functionalization.

5 . The synthetic bioconjugate of claim 1 , wherein the hydrazide group is bonded to the peptide(s) C-terminus, optionally via a spacer.

6 . The synthetic bioconjugate of claim 1 , wherein the hydrazide group is bonded to the peptide(s) N-terminus, optionally via a spacer.

7 . The synthetic bioconjugate of claim 5 , wherein the hydrazide group is bonded to the C-terminus via a spacer comprising one or more amino acids selected from the group consisting of glycine, alanine, arginine, lysine and serine.

8 . The synthetic bioconjugate of claim 6 , wherein the spacer is selected from the group consisting of glycine, glycine-glycine, serine-glycine, lysine-arginine, arginine-arginine, and glycine-serine-glycine.

9 . A composition comprising a synthetic bioconjugate of claim 1 , wherein the average number of peptide(s) per heparin is from about 5 to about 10.

10 . The composition of claim 9 , further comprising additional peptide comprising a collagen-binding unit, where the peptide is non-covalently bound to the synthetic bioconjugate, and further wherein the composition comprises from 1% to about 200% peptide based on the number of disaccharide units in the heparin.

11 . The composition of claim 10 , wherein the additional peptide is ionically bound to the synthetic bioconjugate.

12 . A method for treating a blood vessel in a patient prior to, during, and/or after a vascular injury or intervention, comprising applying an effective amount of a synthetic bioconjugate of claim 1 to the blood vessel.

13 . The method of claim 12 , wherein the synthetic bioconjugate is administered to the patient parenterally.

14 . The method of claim 13 , wherein the parenteral administration is through a route selected from the group consisting of intravascular, intravenous, intraarterial, intramuscular, cutaneous, subcutaneous, percutaneous, intradermal, and intraepidermal.

15 . The method of claim 13 , wherein the synthetic bioconjugate is administered parenterally using a needle or a device for infusion.

16 . The method of claim 12 , wherein the synthetic bioconjugate is administered to the patient with a catheter, as a coating on a balloon, through a porous balloon, or as a coating on a stent.

17 . The method of claim 12 , wherein the intervention is selected from the group consisting of angioplasty, atherectomy, stenting, or other surgical procedure.

18 . The method of claim 12 , wherein the synthetic bioconjugate binds to a denuded vessel in the patient.

19 . The method of claim 12 , wherein the synthetic bioconjugate inhibits platelet activation.

20 . The method of claim 18 , wherein the synthetic bioconjugate inhibits platelet binding to the denuded vessel.

21 . The method of claim 18 , wherein the synthetic bioconjugate inhibits intimal hyperplasia.

22 . The method of claim 18 , wherein the synthetic bioconjugate inhibits thrombosis.

23 . The method of claim 18 , wherein the synthetic bioconjugate inhibits vasospasm.

24 . The method of claim 18 , wherein the synthetic bioconjugate stimulates endothelial cell proliferation.

25 . The method of claim 18 , wherein the synthetic bioconjugate binds to exposed collagen on the denuded vessel.

26 . A method for improving maturation of an arteriovenous fistula (AVF) in a patient in need of hemodialysis, comprising:

applying a solution to the internal wall of a lumen of an AVF; and

restoring or initiating blood flow in the AVF,

wherein the solution comprises an effective amount of a synthetic bioconjugate of claim 1 .

27 . A method for making a synthetic bioconjugate comprising derivatized heparin and from 1 to about 10 peptide(s) comprising an amino acid sequence GELYKSILY (SEQ ID NO: 2), said method comprising contacting heparin, wherein the heparin does not contain oxidatively cleaved saccharide units, with a sufficient amount of peptide, in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), wherein the peptide comprises a hydrazide group, under coupling reaction conditions to provide the synthetic bioconjugate, wherein the peptide(s) and are bound to the heparin via a hydrazide-carbonyl linkage between a terminal hydrazide group on the peptides and a carbonyl group on the derivatized heparin.

28 . The method of claim 27 , wherein the hydrazide group is bonded to the peptide(s) C-terminus, optionally via a spacer.

29 . The method of claim 28 , wherein the spacer comprises one or more amino acids selected from the group consisting of glycine, alanine, arginine, lysine and serine.

30 . The method of claim 29 , wherein the spacer is selected from the group consisting of glycine, glycine-glycine, serine-glycine, arginine-arginine, lysine-arginine, lysine-arginine-arginine and glycine-serine-glycine.