Bothrojaracin, a Bothrops jararaca snake venom-derived (pro)thrombin inhibitor, as an anti-thrombotic molecule.
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.
Zingali
Russolina B
RB
Instituto de Bioquímica Médica, CCS, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. lzingali@bioqmed.ufrj.br
Ferreira
Marcos S
MS
Assafim
Mariane
M
Frattani
Flávia S
FS
Monteiro
Robson Q
RQ
D000818:Animals; D003435:Crotalid Venoms / Q000627:therapeutic use*; D006801:Humans; D051189:Murinae; D012910:Snake Venoms / Q000627:therapeutic use; D013917:Thrombin / Q000037:antagonists & inhibitors*; D020246:Venous Thrombosis / Q000188:drug therapy
D003435:Crotalid Venoms; D012910:Snake Venoms; C083739:bothrojaracin; D013917:Thrombin