Collagen-binding synthetic peptidoglycans, preparation, and methods of use

Abstract

This invention relates to collagen-binding synthetic peptidoglycans and engineered collagen matrices comprising a collagen matrix and a collagen-binding synthetic peptidoglycan where the collagen-binding synthetic peptidoglycan can be aberrant or can have amino acid homology with a portion of the amino acid sequence of a protein or a proteoglycan that regulates collagen fibrillogenesis. The invention also relates to kits, compounds, compositions, and engineered graft constructs comprising such collagen-binding synthetic peptidoglycans or engineered collagen matrices and methods for their preparation and use.

1 - 62 . (canceled) 
     
     
         63 . A peptidoglycan comprising a glycan and from 1 to 50 peptides, wherein the peptides comprise:
 (i) an amino acid sequence having 80% sequence identity to RRANAALKAGELYKSILYGC [SEQ ID NO: 1]; and   (ii) the amino acid sequence GELYKSILY [SEQ ID NO: 17].   
     
     
         64 . The peptidoglycan of  claim 63 , wherein the glycan is a glycosaminoglycan. 
     
     
         65 . The peptidoglycan of  claim 63 , wherein the glycan is alginate, agarose, chondroitin, dermatan, dermatan sulfate, heparan, heparin, keratin, or hyaluronan. 
     
     
         66 . The peptidoglycan of  claim 63 , wherein the glycan is dermatan sulfate. 
     
     
         67 . The peptidoglycan of  claim 63 , wherein the glycan is heparin. 
     
     
         68 . The peptidoglycan of  claim 63 , wherein the peptidoglycan comprises from about 1 to about 10 peptides. 
     
     
         69 . The peptidoglycan of  claim 63 , wherein the peptidoglycan comprises about five peptides. 
     
     
         70 . The peptidoglycan of  claim 63 , wherein the peptides comprise the amino acid sequence RRANAALKAGELYKSILYGS [SEQ ID NO: 18]. 
     
     
         71 . The peptidoglycan of  claim 63 , wherein the peptides are RRANAALKAGELYKSILYGC [SEQ ID NO: 1], and the glycine-cysteine at the C-terminus is optional. 
     
     
         72 . The peptidoglycan of  claim 63 , wherein the peptides are a synthetic peptide having 90% sequence identity to RRANAALKAGELYKSILYGC [SEQ ID NO: 1] and comprises the amino acid sequence GELYKSILY [SEQ ID NO: 17]. 
     
     
         73 . The peptidoglycan of  claim 63 , wherein the peptides are bonded to the glycan via a linker. 
     
     
         74 . The peptidoglycan of  claim 63 , wherein the peptides have up to 40 amino acids. 
     
     
         75 . A peptidoglycan comprising a glycan and from 1 to 50 peptides, wherein the peptides comprise the amino acid sequence RRANAALKAGELYKSILYGS [SEQ ID NO: 18]. 
     
     
         76 . The peptidoglycan of  claim 75 , wherein the glycan is dermatan sulfate or heparin. 
     
     
         77 . The peptidoglycan of  claim 75 , wherein the peptides are bonded to the glycan via a linker. 
     
     
         78 . The peptidoglycan of  claim 75 , wherein the peptides have up to 40 amino acids. 
     
     
         79 . A peptidoglycan comprising a glycan and from 1 to 50 peptides having up to 40 amino acids, wherein:
 (i) the glycan is dermatan sulfate or heparin; and   (ii) the peptides comprise an amino acid sequence having 95% sequence identity to RRANAALKAGELYKSILYGC [SEQ ID NO: 1] and comprises the amino acid sequence GELYKSILY [SEQ ID NO: 17].   
     
     
         80 . The peptidoglycan of  claim 79 , wherein the glycan is dermatan sulfate. 
     
     
         81 . The peptidoglycan of  claim 79 , wherein the glycan is heparin. 
     
     
         82 . The peptidoglycan of  claim 79 , wherein the peptidoglycan comprises from about 1 to about 10 peptides. 
     
     
         83 . The peptidoglycan of  claim 79 , wherein the peptidoglycan comprises about five peptides. 
     
     
         84 . A composition comprising the peptidoglycan of  claim 63  and a pharmaceutically acceptable excipient or diluent, or a combination thereof. 
     
     
         85 . A composition comprising the peptidoglycan of  claim 79  and a pharmaceutically acceptable excipient or diluent, or a combination thereof. 
     
     
         86 . A method of decreasing average fibril diameter in a patient in need thereof, comprising administering to the patient a peptidoglycan comprising a glycan and from 1 to 50 peptides having from 5 to 40 amino acids, wherein the peptides comprise:
 (i) an amino acid sequence having 80% sequence identity to RRANAALKAGELYKSILYGC [SEQ ID NO: 1]; and   (ii) the amino acid sequence GELYKSILY [SEQ ID NO: 17].   
     
     
         87 . The method of  claim 86 , wherein the peptidoglycan is administered in a composition further comprising a pharmaceutically acceptable excipient or diluent, or a combination thereof. 
     
     
         88 . The method of  claim 87 , wherein the composition is formulated for topical administration. 
     
     
         89 . The method of  claim 87 , wherein the composition is formulated for intravenous administration. 
     
     
         90 . A method of inhibiting platelet aggregation in a patient in need thereof, comprising administering to the patient a peptidoglycan comprising a glycan and from 1 to 50 peptides having from 5 to 40 amino acids, wherein the peptides comprise:
 (i) an amino acid sequence having 80% sequence identity to RRANAALKAGELYKSILYGC [SEQ ID NO: 1]; and   (ii) the amino acid sequence GELYKSILY [SEQ ID NO: 17].   
     
     
         91 . A method of inhibiting platelet activation in a patient in need thereof, comprising administering to the patient a peptidoglycan comprising a glycan and from 1 to 50 peptides having from 5 to 40 amino acids, wherein the peptides comprise:
 (i) an amino acid sequence having 80% sequence identity to RRANAALKAGELYKSILYGC [SEQ ID NO: 1]; and   (ii) the amino acid sequence GELYKSILY [SEQ ID NO: 17].