发明名称 |
CHIMERIC TRUNCATED TISSUE PLASMINOGEN ACTIVATOR (t-PA) RESIATANT TO PLASMINOGEN ACTIVATOR INHIBITOR-1 AND IMPROVED BIOCHEMICAL PROPERTIES |
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. |
申请公布号 |
US2015132826(A1) |
申请公布日期 |
2015.05.14 |
申请号 |
US201514594155 |
申请日期 |
2015.01.11 |
申请人 |
Pasteur Institute of Iran (IPI) |
发明人 |
Saadatirad Amirhossein;Mahboudi Fereidoun;Sardari Soroush;Kazemali Mohammadreza;Davami Fatemeh;Majidzadeh Keyvan |
分类号 |
C12N9/72 |
主分类号 |
C12N9/72 |
代理机构 |
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代理人 |
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主权项 |
1. A chimeric truncated tissue plasminogen activator CT t-PA comprising:
a native human t-PA with a F domain, an EGF domain, a K1 domain, a K2 domain and a protease (P) domain; wherein the F domain of native human t-PA is replaced by F domain of vampire bat plasminogen activator, and wherein 24 amino acids (LBS) of the K2 domain are deleted at a position of 202-225, and wherein the amino acids K296, R298, 8299 and R304 in the P domain are replaced by four aspartic acids (DDDD). |
地址 |
Tehran IR |