Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied three fibrin-specific thrombolytic agents in a photochemically-induced, guinea-pig femoral artery model of thrombosis. Tissue-type plasminogen activator (t-PA, 0.3 and 1 mg/kg), single-chain urokinase-type plasminogen activator (scu-PA,5 and 15 mg/kg) and a novel thrombolytic agent, staphylokinase (SAK, 0.3 and 1 mg/kg) were intravenously infused for 30 min after arterial occlusion by a photochemically-induced reaction between rose bengal and light (540 nm). These thrombolytic agents induced thrombolysis in 17-66% of animals and 24 h later, reocclusion occurred in 75-100%. t-PA hardly altered plasma fibrinogen throughout the experimental period. In contrast, scu-PA (15 mg/kg) decreased plasma fibrinogen and alpha 2-antiplasmin levels by 25% and 90% respectively 90 min after beginning the infusion. SAK markedly decreased plasma fibrinogen and alpha 2-antiplasmin levels in dose- and time-dependent manners. These results suggest that this model of thrombosis has a relatively high sensitivity to t-PA, which induced thrombolysis without decreasing fibrinogen and alpha 2-antiplasmin, compared with the other two fibrin-specific thrombolytic agents.
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PMID:A thrombosis model for evaluating thrombolytic agents in the guinea-pig: comparison of t-PA, scu-PA and a novel thrombolytic agent, staphylokinase, on thrombolytic activity. 769 99

We attempted to construct a new recombinant protein characterized by fibrin-specific properties of plasminogen activation combined with antithrombin and antiplatelet activities. To the C-terminal part of recombinant staphylokinase (r-SAK), which is a promising profibrinolytic agent, we assembled: (i) the Kringle 2 domain (K2) of tissue-type plasminogen activator (t-PA), containing a fibrin-specific binding site, (ii) the RGD sequence (Arg-Gly-Asp) for the prevention of platelet aggregation and (iii) the antithrombotic agent - hirudin. The cDNA for hybrid protein SAK-RGD-K2-Hir was cloned into pESP-3 yeast protein expression vector. The introduction of K2 t-PA, RGD sequence and hirudin into r-SAK molecule did not alter the SAK activity. The plasminogen activation rate (determined by K(M) and K(cat)) of SAK-RGD-K2-Hir was not significantly different from that of r-SAK. Affinity and binding strength of the recombinant protein to fibrin immobilized on the biosensor were higher than to r-SAK. We observed a higher clot lysis potency of SAK-RGD-K2-Hir as evidenced by a faster and more profound lysis of 125I-labeled human fibrin clots. The potency of thrombin inhibition by the hirudin part of the recombinant fusion protein SAK-RGD-K2-Hir was the same as that of r-Hir alone. In conclusion, the results of the in vitro study suggest that the SAK-RGD-K2-Hir construct can be a more potent and faster-acting thrombolytic agent with antithrombin and antiplatelet properties compared with standard r-SAK.
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PMID:A new recombinant thrombolytic and antithrombotic agent with higher fibrin affinity--a staphylokinase variant. I. In vitro study. 1615 47