COLLAGEN-BINDING SYNTHETIC PEPTIDOGLYCANS, PREPARATION, AND METHODS OF USE
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].