MODIFIED PROTEIN C AND METHODS OF USE THEREOF

摘要

Modified Protein C molecules have been made which substitute the gamma carboxylglutamic acid (Gla) region of another Vitamin K dependent protein, most preferably prothrombin, for the native region of t he Protein C. A modified Protein C molecules has been made which substitutes the gamma carboxylglutamic acid (Gla) region with the corresponding region of prothrombin. The modified or chimeric protein C has advantages over the wild-type protein C since it is less sensitive to inhibition by some natural antibody inhibitors of protein C (which would otherwise decrease the ability of the protein C to act as an anticoagulant) and which do not need the same cofactors or same amounts of cofactors, and can therefore be effective in patients with lowere d levels of the cofactors such as protein S or the lipids present in elevated levels in platelets such as phosphatidyl ethanolamine (PE). The anticoagulant activity of the chimera was tested in normal and factor V Leiden plasma. The chimera was approximately ten times more effecti ve in inhibiting factor V Leiden plasma clotting.