A new series of the SMTP plasminogen modulator with a phenylglycine-based side chain

摘要

The plasminogen/plasmin system has a central role in blood clot lysis.1 The system is also important in other pathophysiological events, where localized proteolysis is involved.2 Plasminogen is proteolytically activated to plasmin by plasminogen activators through specific cleavage at Arg~(561)-Val~(562). Plasminogen adopts tight conformation due to intramolecular binding of Lys50 and/or Lys62 to the lysine-binding site in the fifth kringle domain.3'4 The tight conformation renders plasminogen less sensitive to activation by plasminogen activators. Plasminogen binding to fibrin or cellular receptors allows relaxation of plasminogen conformation, enabling efficient activation. This mechanism facilitates localized activation of plasminogen and following extracellular proteolysis.