A chimeric streptokinase with unexpected fibrinolytic selectivity

Joel Goldstein, Gary R. Matsueda, Shyh Yu Shaw

研究成果: Article同行評審

5 引文 斯高帕斯(Scopus)


Chimeric 59D8-SK was designed to confer fibrin-selectivity to streptokinase by fusion of the Fab fragment of anti-fibrin antibody 59D8 to the N-terminus of streptokinase (SK: Ile1-Lys414). It was expressed in a mouse hybridoma cell line and purified by affinity chromatography on a 59D8-antigen column. Chimeric 59D8-SK is a disulfide-linked heterodimer composed of an antibody light chain (Mr 27,000) and a N-glycosylated chimeric heavy chain (Mr 90,000). The fibrin targeting by 59D8 increased plasma clot lysis by 2-fold, but connecting 59D8 to SK has provided 59D8-SK several unique properties: (i) 59D8-SK activated human Glu-plasminogen with a significant lag period that coincided with limited proteolysis of 59D8-SK similar to that observed for wild-type SK. In a kinetic study, both gave very similar kinetic parameters for the activation of Glu-plasminogen even though 59D8-SK was N-glycosylated in its SK portion; (ii) 59D8-SK was relatively inactive in human plasma, compared to SK, but it became activated in the presence of clots; (iii) 59D8-SK lysed clots slowly but completely whereas SK lysed clots rapidly but incompletely. Even though the mechanism behind these new properties is not fully understood, they are characteristics of a second-generation plasminogen activator.

頁(從 - 到)429-438
期刊Thrombosis and Haemostasis
出版狀態Published - 1996

All Science Journal Classification (ASJC) codes

  • 血液學


深入研究「A chimeric streptokinase with unexpected fibrinolytic selectivity」主題。共同形成了獨特的指紋。