组织型纤溶酶原激活剂突变体的构建、表达及特性分析

被引：11

作者：

刘士辉

黄培堂

黄翠芬

机构：

[1] 军事医学科学院生物工程研究所

[2] 军事医学科学院生物工程研究所北京

[3] 北京

来源：

中国科学(B辑化学生命科学地学) | 1995年 / 04期

关键词：

组织型纤溶酶原激活剂; 突变体PAI-1;

D O I：

暂无

中图分类号：

R91 [药物基础科学];

学科分类号：

1007 ;

摘要：

利用寡核苷酸诱导的定位突变技术及DNA重组技术构建了组织型纤溶酶原激活剂(t-PA)的PAI-1结合位点Lys296～Gly302缺失的突变体de1(296～302),K1,K2区去糖基化突变体N117Q/N184Q,以及两者的组合突变体GGI,并在COS-7细胞中获得了暂时性表达,并进一步在CHO细胞中稳定表达了组合突变体GGI.在此基础上对表达产物的生物学特性进行了分析,结果显示de1(296～302)和组合突变体GGI获得了PAI-1抗性,组合突变体GGI在与纤维蛋白亲和力未受损害的同时,特异活性约提高46％,半衰期延长约1倍.此组合突变体很可能成为优于野生t-PA的新型溶栓剂候选株.

引用

页码：399 / 405

页数：7

共 12 条

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