Mutant and chimeric recombinant plasminogen activators. Production in eukaryotic cells and preliminary characterization.

Recombinant DNA technology has allowed large-scale production of the physiological, fibrin-specific, plasminogen activators tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA). The results of clinical trials with these agents, mainly for the treatment of acute myocardial infarction, have revealed a limited fibrin specificity at the large therapeutic doses required for efficient thrombolysis. Mutants and variants of t-PA and scu-PA have given important information on structure-function relationships in these proteins and have resulted in rt-PA variants with significantly prolonged half-lives in vivo. Construction of chimaeric plasminogen activators containing various portions of t-PA and scu-PA has produced functionally active enzymes, however with a lower fibrin-affinity than wild-type t-PA. The promise of antibody targeting and the use of synergistic combinations of thrombolytic agents remains to be further investigated. We anticipate that eventually these research lines will yield artificial plasminogen activators with improved efficacy, risk/benefit and cost/benefit ratios.

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Mutant and chimeric recombinant plasminogen activators. Production in eukaryotic cells and preliminary characterization.

Cited by 35 publications

References 48 publications

Fibrinolysis and its Relevance to Acute Focal Cerebral Ischemia

Fibrinolysis and its Relevance to Acute Focal Cerebral Ischemia

The Expression of Tissue-Type Plasminogen Activator and Related Enzymes

New strategies in the development of thrombolytic agents

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