首页> 外国专利> CHIMERIC TRUNCATED TISSUE PLASMINOGEN ACTIVATOR (t-PA) RESIATANT TO PLASMINOGEN ACTIVATOR INHIBITOR-1 AND IMPROVED BIOCHEMICAL PROPERTIES

CHIMERIC TRUNCATED TISSUE PLASMINOGEN ACTIVATOR (t-PA) RESIATANT TO PLASMINOGEN ACTIVATOR INHIBITOR-1 AND IMPROVED BIOCHEMICAL PROPERTIES

机译：嵌合截短的组织中的纤溶酶原激活物（t-PA），与纤溶酶原激活物抑制剂1相关，并改善了其生物化学性质

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摘要

The present invention discloses a thrombolytic therapy for acute myocardial infarction by t-PA. A chimeric truncated form of t-PA is designed and expressed in Pichia pastoris. The new variant t-PA comprises of a finger domain of Desmoteplase, an epidermal growth factor (EGF) domain, a kringle 1 domain, a kringle 2 domain in which the lysine binging site is deleted, and a protease domain where the four amino acids lysine 296, arginine 298, arginine 299, and arginine 304 are substituted by aspartic acid. The chimeric t-PA shows has increased activity of 14 fold in presence of fibrin. The t-PA shows 10-fold increased potency than commercially available full length t-PA (Actylase®) and provides 1.2 fold greater affinity to fibrin. Further a residual activity of only 68% is observed after incubation of Actylase® with PAI-1 and 91% residual activity for t-PA. The t-PA variant is acceptable plasminogen activator with enhanced biochemical properties.

机译：本发明公开了通过t-PA的用于急性心肌梗塞的溶栓治疗。设计了t-PA的嵌合截短形式并在 Pichia pastoris 中表达。新的变体t-PA包含去氨普酶的手指结构域，表皮生长因子（EGF）结构域，kringle 1结构域，klyle 2结构域（其中赖氨酸结合位点被删除）和蛋白酶结构域（其中四个氨基酸）赖氨酸296，精氨酸298，精氨酸299和精氨酸304被天冬氨酸取代。嵌合的t-PA显示在纤维蛋白存在下具有增加的14倍活性。 t-PA的效价比市售全长t-PA（Actylase？）提高了10倍，并且对血纤蛋白的亲和力提高了1.2倍。在与PAI-1一起孵育后，仅观察到68％的残留活性，对t-PA的残留活性为91％。 t-PA变异体是具有增强的生化特性的可接受的纤溶酶原激活剂。 展开▼

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公开/公告号US2015132826A1

专利类型

公开/公告日2015-05-14

原文格式PDF

申请/专利权人 PASTEUR INSTITUTE OF IRAN (IPI);
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申请/专利号US201514594155

发明设计人 KEYVAN MAJIDZADEH;FATEMEH DAVAMI;FEREIDOUN MAHBOUDI;AMIRHOSSEIN SAADATIRAD;SOROUSH SARDARI;MOHAMMADREZA KAZEMALI;
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申请日2015-01-11

分类号C12N9/72;

国家 US

入库时间 2022-08-21 15:26:30

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1. 纤溶酶原激活物抑制剂1(PAI-1)抑制剂和其用途 [P] . 中国专利： CN113056268A . 2021-06-29

2. 纤溶酶原激活物抑制剂1(PAI-1)抑制剂的用途 [P] . 中国专利： CN113056269A . 2021-06-29

3. CHIMERIC TISSUE PLASMINOGEN ACTIVATOR (T-PA) RESIATANT TO PLASMINOGEN ACTIVATOR INHIBITOR-1 AND IMPROVED BIOCHEMICAL PROPERTIES [P] . 美国专利： US2015259666A1 . 2015-09-17

机译：嵌合体组织中的纤溶酶原激活物（T-PA）与纤溶酶原激活物抑制剂1的关系和改善的生物化学性质

4. CHIMERIC TRUNCATED AND MUTANT VARIANT OF TISSUE PLASMINOGEN ACTIVATOR (T-PA) RESISTANT TO PLASMINOGEN ACTIVATOR INHIBITOR-1 [P] . 美国专利： US2012058537A1 . 2012-03-08

机译：抗纤溶酶原激活物抑制剂1的组织纤溶酶原激活物（T-PA）的嵌合截短突变体

5. Assay for plasminogen activator inhibitor-1 and tissue plasminogen activator activity [P] . 美国专利： US6297023B1 . 2001-10-02

机译：纤溶酶原激活物抑制剂-1和组织纤溶酶原激活物活性的测定

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