TARGETING OF PLASMINOGEN ACTIVATORS IN MYOCARDIAL INFARCT

THE LONG-TERM OBJECTIVE OF THIS PROJECT IS THE DEVELOPMENT AND CHARACTERIZATION OF CONJUGATES BETWEEN PLASMINOGEN ACTIVATORS (UROKINASE, TISSUE PLASMINOGEN ACTIVATOR, SINGLE CHAIN UROKINASE) AND MONOCLONAL ANTIBODIES SPECIFIC FOR HUMAN CARDIAC HEAVY CHAIN MYOSIN. THIS TYPE OF CONJUGATE BYSELECTIVELY TARGETING THE PLASMINOGEN ACTIVATOR TO DAMAGED MYOCYTES IN THE AREA OF THE THROMBUS, SHOULD SIGNIFICANTLY REDUCE SYSTEMIC PLASMINOGEN ACTIVATION AND THE ASSOCIATED DELETERIOUS EFFECTS. THE INITIAL PHASE OF THIS RESEARCH WILL BE DIRECTED TOWARD COVALENTLY COUPLING UROKINASE WITH ANTI-MYOSIN ANTIBODIES AND CHARACTERIZING THE RESULTING CONJUGATES FOR PLASMINOGEN ACTIVATING ACTIVITY AND MYOSIN BINDING AVIDITY. IN VITRO TESTING OF THE CONJUGATES WILL BE DONE TO DETERMINE THE DISTANCE FROM THE MYOSIN BINDING SITES WHEREIN PLASMIN PRODUCED BY THE CONJUGATE CAN EFFECT FIBRINOLYSIS. IN ADDITION TO POTENTIAL DEVELOPMENT OF AN IMPROVED THROMBOLYTIC AGENT FOR CLINICAL USE, THESE STUDIES MAY LEAD TO THE DEVELOPMENT OF A MORE GENERAL APPROACH FOR TARGETING SPECIFIC ENZYMES TO PATHOLOGICAL SITES.