Decorin proteoglycan inhibitor of fibrinogen blood clotting
The present invention provides compositions and methods of inhibiting fibrin(ogen) clot formation by utilizing decorin proteoglycan as an anticoagulating and antithrombotic agent. The decorin proteoglycan comprises a decorin core protein or a fragment thereof covalently linked to a galactosaminoglycan polysaccharide. The decorin core protein acts as an anticoagulant and as a carrier for the delivery of an antithrombotic galactosaminoglycan to fibrinogen. Fibrin clotting is inhibited by the decorin proteoglycan in a concentration-dependent fashion.
1. A recombinant anticoagulating and antithrombotic decorin proteoglycan with the sequence of SEQ ID NO: 2 linked to a galactosaminoglycan polysaccharide.
2. The recombinant decorin proteoglycan of claim 1 , wherein said galactosaminoglycan polysaccharide is covalently linked thereto.
3. The recombinant decorin proteoglycan of claim 1 , wherein said proteoglycan comprises a fibrinogen-binding domain.
4. The recombinant decorin proteoglycan of claim 1 , wherein said proteoglycan is chemically derivatized.
5. The recombinant decorin proteoglycan of claim 1 , wherein said galactosaminoglycan polysaccharide comprises heparin, heparan sulfate, chondroitin sulfate or dermatan sulfate or a combination thereof.
6. A pharmaceutical composition comprising the recombinant decorin proteoglycan of claim 1 and a pharmaceutically acceptable carrier.
7. A kit for inhibiting fibrin clot formation, comprising the composition of claim 6 .
8. The kit of claim 7 , further comprising:
an anticoagulating agent, wherein said anticoagulating agent is heparin cofactor II, chondroitin sulfate or dermatan sulfate or a combination thereof.