Derivatives of the human fibrinolytic enzyme pro-urokinase and its analogues having decreased affinity for plasmatic inhibitors are described together with the process for preparing them by recombinant DNA technology. These derivatives demonstrate better enzymatic and fibrinolytic properties than natural pro-urokinase, so providing improved thrombolytic treatment. They are characterized by negatively charged residues in those sites of the pro-urokinase potentially responsible for interaction with plasmatic inhibitors, the presence of the negative charge creating a greater resistance to those inhibitors. Those pro-urokinase derivatives can be modifications either of human pro-urokinase itself or of its analogues, such as mutant- by substitution, deletion, insertion or inversion of human pro-urokinase or of the corresponding enzymes obtained from species other than human, or mammals in general. IMAGE
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