INHIBITION OF METALLOPROTEINASES IN BOTHROPS-ASPER VENOM BY ENDOGENOUS PEPTIDES

Bothrops asper venom contains a variety of degradative enzymes, includ ing metal-ion dependent proteinases as well as low molecular weight pe ptides. Two of these peptides, pyroglutamate-glutamine-tryptophan (pEQ W) and pyroglutamate-asparagine-tryptophan are present in crude venom at concentrations of about 4.5 and 1 mM, respectively. Proteinase frac tions from B. asper are inhibited from digesting oxidized insulin B-ch ain in vitro by both of these tripeptides with an IC50 for pEQW of alm ost-equal-to 0.3 mM. Digestion of purified myotoxin MIII from B. asper venom is also inhibited in vitro by pEQW, suggesting that similar inh ibition of proteinase activities probably occurs in the venom gland. I nhibitory peptides present in venom allow snakes to be protected from their own toxic proteinases and inhibit hydrolysis of venom proteins d uring storage in the venom gland. Upon dilution, such as when venom is injected into prey, peptide inhibitors dissociate from the proteinase and allow their activation. A simple procedure for isolation of these inhibitory peptides is described.