Two-step targeting of urokinase to plasma clot provides efficient fibrinolysis.
Two-step targeting of urokinase to a model thrombus (human plasma clot) has been examined in vitro. To this purpose a covalent conjugate of vector antibodies to fibrinogen with monoclonal non-inhibiting antibody to urokinase was obtained using cross-linking agent disuccinimidilsuberate. After pretreatment with the conjugate clot acquired affinity for urokinase, which alters the character of fibrinolysis. Pretreatment with the conjugate resulted in at least 10-fold decrease in dose of urokinase needed for effective clot lysis (from 150 IU/ml for intact clot to 10-15 IU/ml for pretreated one). This variant of urokinase targeting provides effective clot lysis without fibrinogenolysis in plasma.
Sakharov
D V
DV
Institute of Experimental Cardiology, Cardiology Research Center, Moscow, USSR.
Sinitsyn
V V
VV
Kratasjuk
G A
GA
Popov
N V
NV
Domogatsky
S P
SP
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D005340:Fibrinogen / Q000276:immunology; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D013927:Thrombosis / Q000188:drug therapy*; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D005340:Fibrinogen; D014568:Urokinase-Type Plasminogen Activator