Extracellular matrix-binding synthetic peptidoglycans

Patent metadata

Field	Value
Publication number	US-9872887-B2
Application number	US-201514940990-A
Country	US
Kind code	B2
Filing date	Nov 13, 2015
Priority date	Mar 15, 2013
Publication date	Jan 23, 2018
Grant date	Jan 23, 2018

Abstract

This disclosure provides extracellular matrix-binding synthetic peptidoglycans comprised of one or more synthetic peptides conjugated to a glycan and methods of their use.

First claim

What is claimed is:

1. A method of treating and/or preventing osteoarthritis in a joint of a patient, comprising injecting to the joint an extracellular matrix-binding synthetic peptidoglycan comprising:
a) a glycan;
b) from about 1 to about 80 collagen binding peptide(s); and
c) from about 1 to about 80 hyaluronic acid binding peptide(s);
wherein the peptides of b) and c) are covalently bonded to the glycan.

2. The method of claim 1 , wherein the glycan is dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, or hyaluronic acid.

3. The method of claim 1 , wherein the glycan is dermatan sulfate.

4. The method of claim 1 , wherein the glycan is chondroitin sulfate.

5. The method of claim 1 , wherein the glycan is hyaluronic acid.

6. The method of claim 1 , wherein the peptides are covalently bonded to the glycan via a linker.

7. The method of claim 6 , wherein the linker is N[β-maleimidopropionic acid]hydrazide (BMPH).

8. The method of claim 1 , wherein the synthetic peptidoglycan comprises a total of less than about 50 peptides.

9. The method of claim 1 , wherein the synthetic peptidoglycan comprises a total of from about 10 to about 40 peptides.

10. The method of claim 1 , wherein the synthetic peptidoglycan comprises a total of about 22 peptides.

11. The method of claim 1 , wherein the collagen binding peptide has binding affinity to one or more of collagen types I, II, III, or IV.

12. The method of claim 1 , wherein the collagen binding peptide comprises at least one collagen binding peptide that binds to type I collagen and at least one collagen binding peptide that binds to type II collagen.

13. The method of claim 1 , wherein the collagen binding peptide comprises an amino acid sequence selected from the group consisting of:

i)

(SEQ ID NO: 81)

WYRGRLGC,

(SEQ ID NO: 68)

RRANAALKAGELYKSILYGC,

(SEQ ID NO: 69)

RLDGNEIKRGC,

(SEQ ID NO: 70)

AHEEISTTNEGVMGC,

(SEQ ID NO: 71)

GCGGELYKSILY,

(SEQ ID NO: 72)

NGVFKYRPRYFLYKHAYFYPPLKRFPVQGC,

(SEQ ID NO: 60)

CQDSETRTFY,

(SEQ ID NO: 74)

TKKTLRTGC,

(SEQ ID NO: 75)

GLRSKSKKFRRPDIQYPDATDEDITSHMGC,

(SEQ ID NO: 76)

SQNPVQPGC,

(SEQ ID NO: 77)

SYIRIADTNITGC,

(SEQ ID NO: 64)

SYIRIADTNIT,

(SEQ ID NO: 65)

KELNLVYT,

(SEQ ID NO: 78)

KELNLVYTGC,

(SEQ ID NO: 67)

GSITTIDVPWNV,

(SEQ ID NO: 80)

GELYKSILYGC 

and

(SEQ ID NO: 66)

GSITTIDVPWNVGC,

or
ii) any peptide sequence comprising a sequence with at least about 80% sequence identity to the amino acid sequence of i).

14. The method of claim 1 , wherein the collagen binding peptide is WYRGRLGC (SEQ ID NO: 81), RRANAALKAGELYKSILYGC (SEQ ID NO: 68), RLDGNEIKRGC (SEQ ID NO: 69), AHEEISTTNEGVMGC (SEQ ID NO: 70), GCGGELYKSILY (SEQ ID NO: 71), NGVFKYRPRYFLYKHAYFYPPLKRFPVQGC (SEQ ID NO: 72), CQDSETRTFY (SEQ ID NO: 60), TKKTLRTGC (SEQ ID NO: 74), GLRSKSKKFRRPDIQYPDATDEDITSHMGC (SEQ ID NO: 75), SQNPVQPGC (SEQ ID NO: 76), SYIRIADTNITGC (SEQ ID NO: 77), SYIRIADTNIT (SEQ ID NO: 64), KELNLVYT (SEQ ID NO: 65), KELNLVYTGC (SEQ ID NO: 78), GSITTIDVPWNV (SEQ ID NO: 67), GELYKSILYGC (SEQ ID NO: 80) or GSITTIDVPWNVGC (SEQ ID NO: 66).

15. The method of claim 1 , wherein the collagen binding peptide is WYRGRLGC (SEQ ID NO: 81), or a peptide sequence comprising a sequence with at least about 80% sequence identity to SEQ ID NO: 81.

16. The method of claim 1 , wherein the hyaluronic acid binding peptide comprises an amino acid sequence selected from the group consisting of:

Assignees

• Purdue Research Foundation

Inventors

• Panitch Alyssa
• Paderi John Eric
• Sharma Shaili
• Stuart Katherine Allison
• Vazquez-Portalatin Nelda Marie

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P19/08

  for bone diseases, e.g. rachitism, Paget's disease · CPC title

• A61P17/16

  Emollients or protectives, e.g. against radiation · CPC title