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

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

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

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摘要

The present invention discloses the thrombolytic therapy by t-PA or CT-b for the treatment of the acute myocardial infarction. A chimeric truncated form of t-PA or CT-b is designed and expressed in Pichia pastoris. The CT-b includes desmoteplase finger domain, human EGF, kringle 1 and protease domain. The human kringle 2 domain is removed in CT-b to make it structurally and functionally similar to desmoteplase. The fibrin specificity or the catalytic activity is 1560 times more in the presence of fibrin. The CT-b also shows 1.2 fold higher resistances to PAI-1 enzyme. As the kringle domain is considered as one of the binding sites for PAI-1, the deletion along with amino acid substitution in protease domain contributes to prolonged half-life. Further the activity of the CT-b is intact after exposure to PAI-1. In other words CT-b is inhibited 44% less than t-PA by PAI-1 enzyme, demonstrating improved half life.

机译：本发明公开了通过t-PA或CT-b进行的溶栓治疗，用于治疗急性心肌梗塞。设计了t-PA或CT-b的嵌合截短形式并在 Pichia pastoris 中表达。 CT-b包括去氨普酶手指结构域，人EGF，kringle 1和蛋白酶结构域。在CT-b中去除人kringle 2结构域，使其在结构和功能上类似于去氨普酶。在血纤蛋白存在下，血纤蛋白特异性或催化活性高出1560倍。 CT-b对PAI-1酶的抵抗力也高1.2倍。由于kringle结构域被认为是PAI-1的结合位点之一，因此蛋白酶结构域中的缺失以及氨基酸取代有助于延长半衰期。此外，暴露于PAI-1后，CT-b的活性仍然完整。换句话说，PAI-1酶对CT-b的抑制作用比t-PA低44％，表明半衰期得到改善。 展开▼

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公开/公告号US2015259666A1

专利类型

公开/公告日2015-09-17

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US201514672213

发明设计人 FATEMEH DAVAMI;AMIR HOSSEIN SAADATI;KEIVAN KEIVAN MAJIDZADEH;FEREIDOUN MAHBOUDI;SOROUSH SOROUSH SARDARI;MOHAMMADREZA KAZEMALI;
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申请日2015-03-29

分类号C12N9/72;C07K14/485;

国家 US

入库时间 2022-08-21 15:27:09

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1. 作为纤溶酶原激活物抑制剂1型(PAI－1)的6－(芳基－酰氨基或芳基－酰氨甲基)－萘－2－基氧基－酸衍生物 [P] . 中国专利： CN100467443C . 2009.03.11

2. 作为纤溶酶原激活物抑制剂1型(PAI－1)的6－(芳基－酰氨基或芳基－酰氨甲基)－萘－2－基氧基－酸衍生物 [P] . 中国专利： CN1543453A . 2004-11-03

3. CHIMERIC TRUNCATED TISSUE PLASMINOGEN ACTIVATOR (t-PA) RESIATANT TO PLASMINOGEN ACTIVATOR INHIBITOR-1 AND IMPROVED BIOCHEMICAL PROPERTIES [P] . 美国专利： US2015132826A1 . 2015-05-14

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

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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