Heparan sulfate/heparin mimetics with anti-chemokine and anti-inflammatory activity
The present disclosure provides for methods and compositions comprising a series of synthetic glycopolymers. The disclosure also relates to a kit which is suitable for carrying out the inventive methods.
1. A glycopolymer comprising a plurality of repeating units, wherein each of said repeating units comprises a saccharide moiety (SA), a linking group (L) and a polymer backbone moiety (PB), wherein said repeating units are optionally connected by one or more carbon-carbon double bonds, wherein said glycopolymer is of the formula:
or a pharmaceutically acceptable salt thereof,
wherein:
n is about 35;
R′ and R″ are each independently selected from the group consisting of unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, unsubstituted or substituted cycloalkyl, and unsubstituted or substituted heterocycloalkyl;
each of the repeating unit is of the formula:
R 1 and R 4 are sulfate, and R 2 is sulfite; and
m is 2.
2. The glycopolymer of claim 1 , wherein the polydispersity of said glycopolymer is less than about 4.
3. The glycopolymer of claim 1 , wherein said glycopolymer lacks anti-coagulant activity.
4. A composition comprising a substantially homogeneous population of a glycopolymer of claim 1 .
5. A pharmaceutical composition comprising a glycopolymer of claim 1 , and a pharmaceutically acceptable carrier.
6. A substrate, immobilized thereon a glycopolymer of claim 1 .
7. The glycopolymer of claim 1 , wherein R′ is unsubstituted or substituted cycloalkyl.
8. The glycopolymer of claim 7 , wherein R′ is unsubstituted cycloalkyl.
9. The glycopolymer of claim 1 , wherein R″ is unsubstituted or substituted alkyl.
10. The glycopolymer of claim 9 , wherein R″ is unsubstituted alkyl.
11. The glycopolymer of claim 2 , herein the polydispersity index of said glycopolymer is less than about 1.5.
12. A pharmaceutical composition comprising a glycopolymer of claim 1 , and a second pharmaceutical agent.
13. A kit comprising a glycopolymer of claim 1 .
14. The substrate of claim 6 , wherein said substrate comprises a solid support.
15. The substrate of claim 6 , wherein said substrate is an array.