Activation of Fibrinolysis by SMTP-7 and -8, Novel Staplabin Analogs with a Pseudosymmetric Structure

Abstract

Two novel staplabin analogs, SMTP-7 and -8, have been isolated from cultures of Stachybotrys microspora IFO 30018. Spectroscopic analyses showed that the SMTP-7 molecule consisted of two identical staplabin core structures and ornithine which bridges the two partial structures. In the SMTP-8 molecule, the bridging unit was lysine. At concentrations of 80-150μM, the two compounds caused 2- to 12-fold increase in urokinase-catalyzed plasminogen activation, fibrin binding of plasminogen, and urokinase- and plasminogen-mediated fibrinolysis. These activities of SMTP-7 and -8 were two to ten times higher than those of staplabin and previously isolated SMTPs, which exerted such effects at concentrations ranging from 150 to 800 μM.