HYALURONIC ACID-BINDING SYNTHETIC PEPTIDOGLYCANS, PREPARATION, AND METHODS OF USE

1 . (canceled)

2 . A pharmaceutical composition comprising a synthetic peptidoglycan comprising a glycan and 1 to 20 synthetic peptides conjugated to the glycan, wherein each synthetic peptide is 5 to 40 amino acids in length and comprises a hyaluronic acid-binding amino acid sequence, wherein the glycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, and hyaluronic acid;

wherein each peptide comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2,

wherein X8 is present or is not present,

wherein B1 is a basic amino acid,

wherein B2 is a basic amino acid, and

wherein X1-X8 are non-acidic amino acids;

wherein the composition does not comprise a collagen-binding synthetic peptidoglycan.

3 . A pharmaceutical composition comprising a synthetic peptidoglycan of the formula (P n L) x G

wherein n is 1 to 20;

x is 1 to 20;

L is a linker having an approximate molecular weight of about 20 to about 500 Da; and

P is a synthetic peptide of:

(i) amino acid sequence:

(SEQ ID NO: 2)

GAHWQFNALTVRGG;

(SEQ ID NO: 3)

GDRRRRRMWHRQ;

(SEQ ID NO: 4)

GKHLGGKHRRSR;

(SEQ ID NO: 5)

RGTHHAQKRRS;

(SEQ ID NO: 6)

RRHKSGHIQGSK;

(SEQ ID NO: 7)

SRMHGRVRGRHE;

(SEQ ID NO: 8)

RRRAGLTAGRPR;

(SEQ ID NO: 9)

RYGGHRTSRKWV;

(SEQ ID NO: 10)

RSARYGHRRGVG;

(SEQ ID NO: 11)

GLRGNRRVFARP;

(SEQ ID NO: 12)

SRGQRGRLGKTR;

(SEQ ID NO: 13)

DRRGRSSLPKLAGPVEFPDRKIKGRR;

(SEQ ID NO: 14)

RMRRKGRVKHWG;

(SEQ ID NO: 15)

RGGARGRHKTGR;

(SEQ ID NO: 16)

TGARQRGLQGGWGPRHLRGKDQPPGR;

(SEQ ID NO: 17)

RQRRRDLTRVEG;

(SEQ ID NO: 18)

STKDHNRGRRNVGPVSRSTLRDPIRR;

(SEQ ID NO: 19)

RRIGHQVGGRRN;

(SEQ ID NO: 20)

RLESRAAGQRRA;

(SEQ ID NO: 21)

GGPRRHLGRRGH;

(SEQ ID NO: 22)

VSKRGHRRTAHE;

(SEQ ID NO: 23)

RGTRSGSTR;

(SEQ ID NO: 24)

RRRKKIQGRSKR;

(SEQ ID NO: 25)

RKSYGKYQGR;

(SEQ ID NO: 26)

KNGRYSISR;

(SEQ ID NO: 27)

RRRCGQKKK;

(SEQ ID NO: 28)

KQKIKHVVKLK;

(SEQ ID NO: 29)

KLKSQLVKRK;

(SEQ ID NO: 30)

RYPISRPRKR;

(SEQ ID NO: 31)

KVGKSPPVR;

(SEQ ID NO: 32)

KTFGKMKPR;

(SEQ ID NO: 33)

RIKWSRVSK;

or

(SEQ ID NO: 34)

KRTMRPTRR,

or

(ii) an amino acid sequence having at least 90% sequence identity to an amino acid sequence of (i).

4 . The pharmaceutical composition of claim 2 , wherein the synthetic peptide comprises the amino acid sequence GAHWQFNALTVRGG (SEQ ID NO: 2), or an amino acid sequence having at least about 90% sequence identity to GAHWQFNALTVRGG (SEQ ID NO: 2).

5 . The pharmaceutical composition of claim 2 , comprising 1 to 10 synthetic peptides conjugated to the glycan, wherein each synthetic peptide comprises the amino acid sequence GAHWQFNALTVRGG (SEQ ID NO: 2), or an amino acid sequence having at least about 90% sequence identity to GAHWQFNALTVRGG (SEQ ID NO: 2).

6 . The pharmaceutical composition of claim 2 , wherein the synthetic peptidoglycan comprises from 2 to 20 of the synthetic peptides.

7 . The pharmaceutical composition of claim 2 , wherein the synthetic peptidoglycan comprises from 5 to 15 of the synthetic peptides.

8 . The pharmaceutical composition of claim 2 , wherein the synthetic peptides are covalently conjugated to the glycan.

9 . The pharmaceutical composition of claim 8 , wherein the synthetic peptides are covalently conjugated to the glycan through a linker having an approximate molecular weight of about 20 to about 500 Da.

10 . The pharmaceutical composition of claim 2 , wherein each synthetic peptide is separately conjugated to the glycan.

11 . A pharmaceutical composition comprising a glycan and 1 to 10 synthetic peptides conjugated to the glycan, wherein each synthetic peptide has the sequence of GAHWQFNALTVRGG (SEQ ID NO: 2) or an amino acid sequence having at least 90% sequence identity to GAHWQFNALTVRGG (SEQ ID NO: 2), wherein the glycan is chondroitin sulfate.

12 . A method of treatment for arthritis in a patient, said method comprising administering to the patient an effective amount of the pharmaceutical composition of claim 2 .

13 . The method of claim 12 wherein each synthetic peptide comprises:

(i) an amino acid sequence selected from the group consisting of:

(SEQ ID NO: 2)

GAHWQFNALTVRGG;

(SEQ ID NO: 3)

GDRRRRRMWHRQ;

(SEQ ID NO: 4)

GKHLGGKHRRSR;

(SEQ ID NO: 5)

RGTHHAQKRRS;

(SEQ ID NO: 6)

RRHKSGHIQGSK;

(SEQ ID NO: 7)

SRMHGRVRGRHE;

(SEQ ID NO: 8)

RRRAGLTAGRPR;

(SEQ ID NO: 9)

RYGGHRTSRKWV;

(SEQ ID NO: 10)

RSARYGHRRGVG;

(SEQ ID NO: 11)

GLRGNRRVFARP;

(SEQ ID NO: 12)

SRGQRGRLGKTR;

(SEQ ID NO: 13)

DRRGRSSLPKLAGPVEFPDRKIKGRR;

(SEQ ID NO: 14)

RMRRKGRVKHWG;

(SEQ ID NO: 15)

RGGARGRHKTGR;

(SEQ ID NO: 16)

TGARQRGLQGGWGPRHLRGKDQPPGR;

(SEQ ID NO: 17)

RQRRRDLTRVEG;

(SEQ ID NO: 18)

STKDHNRGRRNVGPVSRSTLRDPIRR;

(SEQ ID NO: 19)

RRIGHQVGGRRN;

(SEQ ID NO: 20)

RLESRAAGQRRA;

(SEQ ID NO: 21)

GGPRRHLGRRGH;

(SEQ ID NO: 22)

VSKRGHRRTAHE;

(SEQ ID NO: 23)

RGTRSGSTR;

(SEQ ID NO: 24)

RRRKKIQGRSKR;

(SEQ ID NO: 25)

RKSYGKYQGR;

(SEQ ID NO: 26)

KNGRYSISR;

(SEQ ID NO: 27)

RRRCGQKKK;

(SEQ ID NO: 28)

KQKIKHVVKLK;

(SEQ ID NO: 29)

KLKSQLVKRK;

(SEQ ID NO: 30)

RYPISRPRKR;

(SEQ ID NO: 31)

KVGKSPPVR;

(SEQ ID NO: 32)

KTFGKMKPR;

(SEQ ID NO: 33)

RIKWSRVSK;

and

(SEQ ID NO: 34)

KRTMRPTRR,

or

(ii) an amino acid sequence having at least 90% sequence identity to an amino acid sequence of (i).

14 . The method of claim 12 wherein the synthetic peptidoglycan is resistant to aggrecanase.

15 . The method of claim 12 wherein each synthetic peptide has a glycine-cysteine attached to the C-terminus of the peptide

16 . The method of claim 12 wherein the arthritis is selected from the group consisting of osteoarthritis and rheumatoid arthritis.

17 . The method of claim 12 wherein the dosage of the synthetic peptidoglycan is in a concentration ranging from about 0.1 μM to about 10 μM.

18 . A method of treatment for arthritis in a patient, said method comprising administering to the patient an effective amount of a pharmaceutical composition comprising a glycan and 1 to 10 synthetic peptides conjugated to the glycan, wherein each synthetic peptide has the sequence of GAHWQFNALTVRGG (SEQ ID NO: 2) or an amino acid sequence having at least 90% sequence identity to GAHWQFNALTVRGG (SEQ ID NO: 2), wherein the glycan is chondroitin sulfate; and wherein the composition does not comprise a collagen-binding synthetic peptidoglycan.

19 . The method of claim 18 , wherein the synthetic peptides are covalently conjugated to the glycan through a linker having an approximate molecular weight of about 20 to about 500 Da.