[发明专利]一种溶栓酶及其制备方法和应用

摘要

本发明涉及一种新溶栓酶，使用溶栓酶已成为治疗心肌梗塞和脑血栓疾病的标准疗法。新溶栓酶来源于人类大脑，是经重组基因克隆所获得的新溶栓酶。该分子由大肠杆菌生产。新溶栓酶基因克隆于T7启动子和lac调控下表达。在DnaY的辅助下，新溶栓酶表达量为细胞总蛋白的35％以上。新溶栓酶具有组织型纤溶酶原激活剂tPA的优点，如血栓特异性的同时，在药理、药代和药效上优于tPA。新溶栓酶的半衰期为15至23分钟，而tPA只有3.5分钟。

主权项

1、一种溶栓酶，其特征在于所述的溶栓酶由395个氨基酸组成，其序列如下：MetAlaSerCysArgAspGluLysThrGln10MetIleTyrGlnGlnHisGlnSerTrpLeu20ArgProValLeuArgSerAsnArgValGlu30TyrCsyTrpCysAsnSerGlyArgAlaGln40CysSerGluGlyAsnSerAspCysTyrPhe50GlyAsnGlySerAlaTyrArgGlyThrHis60SerLeuThrGluSerGlyAlaSerCysLeu70ProTrpAsnSerMetIleLeuIleGlyLys80ValTyrThrAlaGlnAsnProSerAlaGln90AlaLeuGlyLeuGlyLysHisAsnTyrCys100ArgAsnProAspGlyAspAlaLysProTrp110CysHisValLeuLysAspArgArgLeuThr120TrpGluTyrCysAspValProSerCysSer130ThrCysGlyLeuArgGlnTyrSerGlnPro140GlnPheArgIleLysGlyGlyLeuPheAla150AspIleAlaSerHisProTrpGlnAlaAla160IlePheAlaLysHisGluGluSerProGly170GluArgPheLeuCysGlyGlyIleLeuIle180SerSerCysTrpIleLeuSerAlaAlaHis190CysPheGlnGluArgPheProProHisHis200LeuThrValIleLeuGlyLeuTheTyrArg210ValTyrProGlyGluGluGluGlnLysPhe220GluValGluLysTyrIleValHisLysGlu230PheAspAspAspThrTyrAspAsnAspIle240AlaLeuLeuGlnLeuLysSerAspSerSer250ArgCysAlaGlnGluSerSerValValArg260ThrValCysLeuProProAlaAspLeuGln270LeuProAspTrpThrGluCysGluLeuSer280GlyTyrGlyLysHisGluAlaLeuSerPro290PheTyrSerGluArgLeuLysGluAlaHis300ValArgLeuTyrProSerSerArgCysThr310SerGlnHisLeuLeuAsnArgThrValThr320AspAsnMetLeuCysAlaGlyAspThrArg330SerGlyGlyPheGlnAlaAsnLeuHisAsp340AlaCysGlnGlyAspSerGlyGlyProLeu350ValCysLeuAsnAspGlyArgMetThrLeu360ValGlyIleIleSerTrpGlyLeuGlyCys370GlyGlnLysAspValProGlyValTyrThr380LysValThrAsnTyrLeuAspTrpIleArg390AspAsnMetArgPro395