Summary
MDL 28,050 is a decapeptide antithrombin agent that inhibits a-thrombin-induced fibrin clot formation by binding to a non-catalytic site on α-thromhin. It is the result of chemical and structural optimization of a functional domain of the leech anticoagulant, hirudin. In contrast to the contention that the polyanionic nature of this C-terminal functional domain governs its interaction with α-thrombin, systematic study of this region has shown the importance of the lipophilic residues for providing the functionality necessary foi potent binding to a-thrombin. The development of MDL 28,050 and other effective antithrombin agents are outlined through the description of the structure-activity relationships (SAR) for these peptides. These peptides are effective in a variety of in vitro and in vivo models of thrombosis.
