Hyaluronic acid-binding synthetic peptidoglycans, preparation, and methods of use

1. 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, and wherein the glycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, and keratan sulfate.

2. The synthetic peptidoglycan of claim 1 wherein each synthetic 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.

3. The synthetic peptidoglycan of claim 1 wherein each synthetic peptide comprises:

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

GAHWQFNALTVRGG;

(SEQ ID NO: 2)

GDRRRRRMWHRQ;

(SEQ ID NO: 3)

GKHLGGKHRRSR;

(SEQ ID NO: 4)

RGTHHAQKRRS;

(SEQ ID NO: 5)

RRHKSGHIQGSK;

(SEQ ID NO: 6)

SRMHGRVRGRHE;

(SEQ ID NO: 7)

RRRAGLTAGRPR;

(SEQ ID NO: 8)

RYGGHRTSRKWV;

(SEQ ID NO: 9)

RSARYGHRRGVG;

(SEQ ID NO: 10)

GLRGNRRVFARP;

(SEQ ID NO: 11)

SRGQRGRLGKTR;

(SEQ ID NO: 12)

DRRGRSSLPKLAGPVEFPDRKIKGRR;

(SEQ ID NO: 13)

RMRRKGRVKHWG;

(SEQ ID NO: 14)

RGGARGRHKTGR;

(SEQ ID NO: 15)

TGARQRGLQGGWGPRHLRGKDQPPGR;

(SEQ ID NO: 16)

RQRRRDLTRVEG;

(SEQ ID NO: 17)

STKDHNRGRRNVGPVSRSTLRDPIRR;

(SEQ ID NO: 18)

RRIGHQVGGRRN;

(SEQ ID NO: 19)

RLESRAAGQRRA;

(SEQ ID NO: 20)

GGPRRHLGRRGH;

(SEQ ID NO: 21)

VSKRGHRRTAHE;

(SEQ ID NO: 22)

RGTRSGSTR;

(SEQ ID NO: 23)

RRRKKIQGRSKR;

(SEQ ID NO: 24)

RKSYGKYQGR;

(SEQ ID NO: 25)

KNGRYSISR;

(SEQ ID NO: 26)

RRRCGQKKK;

(SEQ ID NO: 27)

KQKIKHVVKLK;

(SEQ ID NO: 28)

KLKSQLVKRK;

(SEQ ID NO: 29)

RYPISRPRKR;

(SEQ ID NO: 30)

KVGKSPPVR;

(SEQ ID NO: 31)

KTFGKMKPR;

(SEQ ID NO: 32)

RIKWSRVSK;

(SEQ ID NO: 33)

and

KRTMRPTRR, or

(SEQ ID NO: 34)

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

4. The synthetic peptidoglycan of claim 1 , wherein at least a 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 synthetic peptidoglycan of claim 4 , wherein each glycan is conjugated to about 10 synthetic peptides.

6. A synthetic peptidoglycan comprising a glycan and 1 to 20 synthetic peptides covalently 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.

7. The synthetic peptidoglycan of claim 6 , wherein the synthetic peptides are covalently conjugated to the glycan through a linker.

8. The synthetic peptidoglycan of claim 6 , 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.

9. The synthetic peptidoglycan of claim 6 wherein each synthetic peptide comprises:

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

GAHWQFNALTVRGG;

(SEQ ID NO: 2)

GDRRRRRMWHRQ;

(SEQ ID NO: 3)

GKHLGGKHRRSR;

(SEQ ID NO: 4)

RGTHHAQKRRS;

(SEQ ID NO: 5)

RRHKSGHIQGSK;

(SEQ ID NO: 6)

SRMHGRVRGRHE;

(SEQ ID NO: 7)

RRRAGLTAGRPR;

(SEQ ID NO: 8)

RYGGHRTSRKWV;

(SEQ ID NO: 9)

RSARYGHRRGVG;

(SEQ ID NO: 10)

GLRGNRRVFARP;

(SEQ ID NO: 11)

SRGQRGRLGKTR;

(SEQ ID NO: 12)

DRRGRSSLPKLAGPVEFPDRKIKGRR;

(SEQ ID NO: 13)

RMRRKGRVKHWG;

(SEQ ID NO: 14)

RGGARGRHKTGR;

(SEQ ID NO: 15)

TGARQRGLQGGWGPRHLRGKDQPPG

(SEQ ID NO: 16)

RQRRRDLTRVEG;

(SEQ ID NO: 17)

STKDHNRGRRNVGPVSRSTLRDPIRR;

(SEQ ID NO: 18)

RRIGHQVGGRRN;

(SEQ ID NO: 19)

RLESRAAGQRRA;

(SEQ ID NO: 20)

GGPRRHLGRRGH;

(SEQ ID NO: 21)

VSKRGHRRTAHE;

(SEQ ID NO: 22)

RGTRSGSTR;

(SEQ ID NO: 23)

RRRKKIQGRSKR;

(SEQ ID NO: 24)

RKSYGKYQGR;

(SEQ ID NO: 25)

KNGRYSISR;

(SEQ ID NO: 26)

RRRCGQKKK;

(SEQ ID NO: 27)

KQKIKHVVKLK;

(SEQ ID NO: 28)

KLKSQLVKRK;

(SEQ ID NO: 29)

RYPISRPRKR;

(SEQ ID NO: 30)

KVGKSPPVR;

(SEQ ID NO: 31)

KTFGKMKPR;

(SEQ ID NO: 32)

RIKWSRVSK;

(SEQ ID NO: 33)

and

KRTMRPTRR, or

(SEQ ID NO: 34)

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

10. A method for treating arthritis in a patient in need thereof, said method comprising administering to the patient a synthetic peptidoglycan of claim 6 .

11. A method of treatment for arthritis in a patient, said method comprising administering to the patient 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, and wherein the glycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, and keratan sulfate.

12. The method of claim 11 wherein each synthetic 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.

13. The method of claim 11 wherein each synthetic peptide comprises:

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

GAHWQFNALTVRGG;

(SEQ ID NO: 2)

GDRRRRRMWHRQ;

(SEQ ID NO: 3)

GKHLGGKHRRSR;

(SEQ ID NO: 4)

RGTHHAQKRRS;

(SEQ ID NO: 5)

RRHKSGHIQGSK;

(SEQ ID NO: 6)

SRMHGRVRGRHE;

(SEQ ID NO: 7)

RRRAGLTAGRPR;

(SEQ ID NO: 8)

RYGGHRTSRKWV;

(SEQ ID NO: 9)

RSARYGHRRGVG;

(SEQ ID NO: 10)

GLRGNRRVFARP;

(SEQ ID NO: 11)

SRGQRGRLGKTR;

(SEQ ID NO: 12)

DRRGRSSLPKLAGPVEFPDRKIKGRR;

(SEQ ID NO: 13)

RMRRKGRVKHWG;

(SEQ ID NO: 14)

RGGARGRHKTGR;

(SEQ ID NO: 15)

TGARQRGLQGGWGPRHLRGKDQPPGR;

(SEQ ID NO: 16)

RQRRRDLTRVEG;

(SEQ ID NO: 17)

STKDHNRGRRNVGPVSRSTLRDPIRR;

(SEQ ID NO: 18)

RRIGHQVGGRRN;

(SEQ ID NO: 19)

RLESRAAGQRRA;

(SEQ ID NO: 20)

GGPRRHLGRRGH;

(SEQ ID NO: 21)

VSKRGHRRTAHE;

(SEQ ID NO: 22)

RGTRSGSTR;

(SEQ ID NO: 23)

RRRKKIQGRSKR;

(SEQ ID NO: 24)

RKSYGKYQGR;

(SEQ ID NO: 25)

KNGRYSISR;

(SEQ ID NO: 26)

RRRCGQKKK;

(SEQ ID NO: 27)

KQKIKHVVKLK;

(SEQ ID NO: 28)

KLKSQLVKRK;

(SEQ ID NO: 29)

RYPISRPRKR;

(SEQ ID NO: 30)

KVGKSPPVR;

(SEQ ID NO: 31)

KTFGKMKPR;

(SEQ ID NO: 32)

RIKWSRVSK;

(SEQ ID NO: 33)

and

KRTMRPTRR, or

(SEQ ID NO: 34)

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

14. The method of claim 11 , wherein the synthetic peptidoglycan is resistant to aggrecanase.

15. The method of claim 11 , wherein the peptide component of the synthetic peptidoglycan has a glycine-cysteine attached to the C-terminus of the peptide.

16. The method of claim 11 , wherein the arthritis is selected from the group consisting of osteoarthritis and rheumatoid arthritis.

17. The method of claim 11 , wherein the synthetic peptidoglycan is in a concentration ranging from about 0.1 μM to about 10 μM.