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 demonstra...
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Published in | European journal of pharmacology Vol. 566; no. 1; pp. 137 - 144 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Amsterdam
Elsevier B.V
02.07.2007
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0014-2999 1879-0712 |
DOI: | 10.1016/j.ejphar.2007.03.010 |