Functional Properties of a Novel Mutant of Staphylokinase with Platelet-targeted Fibrinolysis and Antiplatelet Aggregation Activities.
From: 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.
European journal of pharmacology
- Publish Date: Jul 2007
- ISSN: 0014-2999
- Volume: 566
- Issue: 1-3
- Pages: 137-44
- Medium: Print
- Language: English
- Citation (JAMA): Chen Hongshan, Mo Wei, Zhang Yanling, et al. Functional Properties of a Novel Mutant of Staphylokinase with Platelet-targeted Fibrinolysis and Antiplatelet Aggregation Activities.. Eur. J. Pharmacol. Jul 2007;566:137-44
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.
Mesh Headings (Keywords): Animals, Coronary Thrombosis, Fibrin, Fibrinolysis, Humans, Metalloendopeptidases, Mutation, Plasminogen, Platelet Aggregation, Platelet Aggregation Inhibitors, Swine
Check for Full Text / PubMed Unique Identifier (PMID): 17451675
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