title: Functional properties of a novel mutant of staphylokinase with platelet-targeted fibrinolysis and antiplatelet aggregation activities.
abstract: The present study was performed to characterize the functional properties of RGD-SAK, a novel mutant of staphylokinase (SAK). Biochemical analysis indicated that RGD-SAK maintained the similar structure and the fibrinolytic function of SAK. Measurement of platelet binding activity in vitro demonstrated that RGD-SAK had a much higher affinity with platelets than SAK. In vitro platelet-rich clot lysis assay demonstrated that the engineered mutant outperformed the non-manipulated SAK. The time required for 50% platelet-rich clot lysis was reduced significantly across different concentrations of RGD-SAK comparing with SAK. Meanwhile, RGD-SAK was found to inhibit ADP-induced platelet aggregation in a concentration-dependent manner while SAK had negligible effect on platelet aggregation. In concordance, further study in a porcine coronary balloon injury model demonstrated the efficacy of RGD-SAK for the lysis of platelet-rich coronary blood clots and for the prevention of reocclusion after thrombolysis. These results suggested that RGD-SAK may serve as a potential thrombolytic agent with platelet-targeted fibrinolysis and antiplatelet aggregation activities.
authors: The Key Laboratory of Molecular Medicine, Ministry of Education, Dong' an Road 130#, Fudan university, and Department of Cardiology, Zhongshan Hospital, Shanghai, 200032, P.R. China.
authors: Hongshan
authors: H
authors: Chen
authors: Wei
authors: W
authors: Mo
authors: Yanling
authors: Y
authors: Zhang
authors: Huabo
authors: H
authors: Su
authors: Janying
authors: J
authors: Ma
authors: Ruiming
authors: R
authors: Yao
authors: Shaoheng
authors: S
authors: Zhang
authors: Junbo
authors: J
authors: Ge
authors: Houyan
authors: H
authors: Song
mesh_terms: D000818:Animals; D003328:Coronary Thrombosis / Q000188:drug therapy* / Q000503:physiopathology; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D009154:Mutation; D010958:Plasminogen / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013552:Swine
chemical_list: D010975:Platelet Aggregation Inhibitors; D005337:Fibrin; D010958:Plasminogen; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus