Functional properties of a novel mutant of staphylokinase with platelet-targeted fibrinolysis and antiplatelet aggregation activities.
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.
Chen
Hongshan
H
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.
Mo
Wei
W
Zhang
Yanling
Y
Su
Huabo
H
Ma
Janying
J
Yao
Ruiming
R
Zhang
Shaoheng
S
Ge
Junbo
J
Song
Houyan
H
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
D010975:Platelet Aggregation Inhibitors; D005337:Fibrin; D010958:Plasminogen; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus