Antibiotic A10255 (Thioplabin) enchances fibrin binding and activation of plasminogen

Abstract

Three thiopeptide metabolites that enhance fibrin binding of plasminogen were isolated from a culture of Streptomyces sp. R1401. A combination of spectroscopic analyses revealed that these compounds were identical with the antibiotic A10255B, E and G. These agents enhanced fibrin binding of plasminogen and plasminogen/urokinase-mediated fibirinolysis at concentrations of 5-20 μM. A10255B reversibily increased urokinase-catalyzed activation of plasminogen by lowering Km, while the agent did not enhance urokinase activity when substrates other than plasminogen were used, indicating that the agent affects plasminogen to increase its affinity to urokinase. A smaller but significant increase in activation was also observed when conformationally relaxed plasminogen derivatives such as Lys-plasminogen and mini-plasminogen were used. Two related thiopeptide antibiotics with a C-terminal amide had no effect on plasminogen activation, suggesting a role of the terminal carboxyl of the A10255 molecule in activity.