发明名称 |
PROTEASE-ACTIVATABLE PSEUDOMONAS EXOTOXIN A-LIKE PROPROTEINS |
摘要 |
This invention provides protease-activatable Pseudomonas exotoxin A-like ("PElike") proproteins. The proproteins comprise (1) a cell recognition domain of between 10 and 1500 amino acids that binds to a cell surface receptor; (2) a modified PE translocation domain comprising an amino acid sequence sufficiently homologous to domain II of PE to effect translocation to a cell cytosol upon proteolytic cleavage, wherein the translocation domain comprises a cysteine-cysteine loop that comprises a protease activatable sequence cleavable by a protease and wherein the cysteine-cysteine loop is substantially un-activatable by furin; (3) optionally, a PE Ib-like domain comprising an amino acid sequence up to 1500 amino acids; (4) a cytotoxicity domain comprising an amino acid sequence substantially homologous to domain III of PE, the cytotoxicity domain having ADP-ribosylating activity; and (5) an endoplasmic reticulum ("ER") retention sequence. The invention also provides methods of using these proproteins for killing target cells.
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申请公布号 |
CA2271291(A1) |
申请公布日期 |
1998.05.14 |
申请号 |
CA19972271291 |
申请日期 |
1997.11.05 |
申请人 |
THE GOVERNMENT OF THE UNITED STATES OF AMERICA, REPRESENTED BY THE SECRE TARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES |
发明人 |
PASTAN, IRA;REITER, YORAM;FITZGERALD, DAVID J. |
分类号 |
C12N15/09;A61K38/00;A61K47/48;A61P35/00;C07K14/21;C07K16/30;C07K19/00;C12N15/31;C12P21/04;(IPC1-7):C12N15/31;C12P21/06;A61K39/104;C12N15/62 |
主分类号 |
C12N15/09 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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