Gamma-prime fibrinogen is an isoform of the blood clotting factor fibrinogen that is a newly-emerging cardiovacular disease risk factor. This application's long- term goal is to elucidate the genetic regulation of gamma-prime fibrinogen as a foundation for understanding its role in cardiovascular disease.
"The anticoagulant (Gammarin) is a synthetic peptide that corresponds in amino acid sequence to the carboxyl terminal 18 amino acids in the g' chain of the blood clotting factor fibrinogen, PEHPAETEYDSLYPEDDL, but contains phosphotyrosine residues in place of the natural sulfotyrosine residues at amino acids 9 and 13 (equivalent to amino acids 418 and 422 in the native g' chain). Gammarin binds to exosite II on thrombin (Lovely 2003; Sabo 2006), similar to heparin, but unlike heparin, Gammarin inhibits the action of thrombin even in the absence of the natural thrombin inhibitor antithrombin III. We have shown that Gammarin inhibits thrombosis in a baboon model (Lovely 2007), and prevents activation of hemophilia factor A (factor VIII), while allowing normal platelet adhesion for primary hemostasis." Inventors:
David Farrell and