Bothrojaracin, a Bothrops jararaca snake venom-derived (pro)thrombin inhibitor, as an anti-thrombotic molecule |
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Authors: | Zingali Russolina B Ferreira Marcos S Assafim Mariane Frattani Flávia S Monteiro Robson Q |
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Institution: | Instituto de Bioquímica Médica, CCS, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. lzingali@bioqmed.ufrj.br |
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Abstract: | Bothrojaracin (BJC) is a selective and potent thrombin inhibitor (KD = 0.6 nM) which also binds to prothrombin on proexosite I (KD = 175 nM). Incubation of BJC with human or rat plasma produced a band that co-migrates with purified prothrombin-BJC complex. We further analyzed the in vivo anti-thrombotic effect of BJC on a venous thrombosis model in rats that combines stasis and hypercoagulability. The administration of 1 mg/kg (i.v.) doses of BJC decreased thrombus weight by approximately 95%. Evaluation of the in vivo effect of BJC in mice using a pulmonary thromboembolism model induced by thrombin showed that BJC protects 100% of mice from death. Altogether, our data show that BJC is a potent anti-thrombotic agent that could further help the development of new prothrombin-directed drugs. |
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