发明申请
US20150259666A1 CHIMERIC TISSUE PLASMINOGEN ACTIVATOR (T-PA) RESIATANT TO PLASMINOGEN ACTIVATOR INHIBITOR-1 AND IMPROVED BIOCHEMICAL PROPERTIES
审中-公开

基本信息:
- 专利标题: CHIMERIC TISSUE PLASMINOGEN ACTIVATOR (T-PA) RESIATANT TO PLASMINOGEN ACTIVATOR INHIBITOR-1 AND IMPROVED BIOCHEMICAL PROPERTIES
- 专利标题(中):CHMERIC TISSUE PLASMINOGEN ACTIVATOR(T-PA)RESOATANT TO PLASMINOGEN ACTIVATOR INHIBITOR-1和改进的生物化学性质
- 申请号:US14672213 申请日:2015-03-29
- 公开(公告)号:US20150259666A1 公开(公告)日:2015-09-17
- 发明人: MohammadReza Kazemali , Amir Hossein Saadati , Keivan Keivan Majidzadeh , Soroush Soroush Sardari , Fatemeh Davami , Fereidoun Mahboudi
- 申请人: Pasteur Institute of Iran (IPI)
- 主分类号: C12N9/72
- IPC分类号: C12N9/72 ; C07K14/485
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.
摘要(中):
本发明公开了用于治疗急性心肌梗死的t-PA或CT-b的溶栓治疗。 在巴斯德毕赤酵母中设计并表达t-PA或CT-b的嵌合截短形式。 CT-b包括desmoteplase指结构域,人EGF,kringle 1和蛋白酶结构域。 在CT-b中除去人类kringle 2结构域,使其在结构和功能上类似于去米他普酶。 纤维蛋白特异性或催化活性在纤维蛋白存在下为1560倍。 CT-b还显示出对PAI-1酶的1.2倍高的抗性。 由于三环结构域被认为是PAI-1的结合位点之一,因此在蛋白酶结构域中缺失与氨基酸取代有关,延长半衰期。 此外,CT-b的活性在暴露于PAI-1后是完整的。 换句话说,通过PAI-1酶,CT-b比t-PA抑制44%,显示出改善的半衰期。