Functional properties of a novel mutant of staphylokinase with platelet-targeted fibrinolysis and antiplatelet aggregation activities

Hongshan Chen, Wei Mo, Yanling Zhang, Huabo Su, Janying Ma, Ruiming Yao, Shaoheng Zhang, Junbo Ge, Houyan Song

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)137-144
Number of pages8
JournalEuropean Journal of Pharmacology
Volume566
Issue number1-3
DOIs
StatePublished - Jul 2 2007
Externally publishedYes

Keywords

  • Antiplatelet activity
  • Platelet-targeted fibrinolysis
  • RGD motif
  • Staphylokinase

ASJC Scopus subject areas

  • Pharmacology

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