| 摘要 |
New protease-resistant single-chain urokinase derivatives are provided. In particular, derivatives are provided in which the Lys135, Lys136 and Arg156 to Lys158 sites are blocked or modified covalently so as to be less susceptible to proteolytic cleavage. The preferred covalent modifications are variants of the amino acid sequence at the sites where proteolysis of urokinase occurs. These are produced optically by synthesis of single-chain urokinase mutants in recombinant cell culture. The new urokinase derivatives of the present invention offer the advantage of avoiding the substantial generation of double-chain urokinase, either in vivo or during recombinant cell culture. However, the derivatives still activate plasminogen in blood clot lysis initiation.
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