Synthesis of taurine- and/or acetyl group-conjugated poly(D-Glu, D-Lys) derivatives and their effects on fibrinolysis

Abstract

A series of C-sulfoethylated and/or N-acetylated poly(D-Glu, D-Lys) (polyGL) derivatives was synthesized and their effects on tissue-type plasminogen activator (t-PA)-induced fibrinolysis were investigated. These derivatives accelerated t-PA-induced plasma (fibrin) clot lysis and t-PA-catalyzed plasminogen activation with the following order of potency: C-sulfoethylated and N-acetylated polyGL > N-acetylated polyGL > C-sulfoethylated polyGL > polyGL. The most potent stimulator C-sulfoethylated and N-acetylated polyGL associated with both t-PA and plasminogen under low ionic conditions, whereas it did not prevent the bindings of t-PA and plasminogen to fibrin. These results suggest that t-PA and plasminogen preferentially bind to sulfated or carboxylated polyanions, which may be required to possess certain neutral groups, and such complex formation may improve the plasminogen activation kinetics in a different manner from that of fibrin.