A Latent Inhibitor of Fibrin Polymerization with Ancillary Anticoagulant Activity

Abstract

The polymerization of fibrin is known to be initiated by a set of knob-hole interactions involving amino-terminal residues exposed by the thrombin-dependent release of the fibrinopeptide A, on the one hand, and complementary sites on the terminal γ-chain domains, on the other hand (reviewed by Doolittle [1]). Synthetic peptides based on the newly uncovered sequence of the fibrin α chain (Gly-Pro-Arg-) are effective inhibitors of fibrin formation [2,3]. The association constants of these synthetic knobs are not very large, however, and as a result of their small size the peptides are rapidly cleared from the circulation in vivo. Efforts to make peptide derivatives that bind effectively to albumin while still maintaining their antipolymerant activity have only been modestly successful [4].