Design, synthesis, and evaluation of venom serine protease peptidic inhibitors.

BACKGROUND

In Central and South America, snakebite envenomation is mainly caused by spp. snakes, whose venoms feature significant biochemical richness, including serine proteases. The available bothropic antivenoms are efficient in avoiding fatalities, but do not completely neutralize venom serine proteases, which are co-responsible for some disorders observed during envenomation.

METHODS

In order to search for tools to improve the antivenom's, 6-mer peptides were designed based on a specific substrate for venom serine proteases, and then synthesized, with the intention to selectively inhibit these enzymes.

RESULTS

Using batroxobin as a snake venom serine protease model, two structurally similar inhibitor peptides were identified. When tested on venom, one of the new inhibitors displayed a good potential to inhibit the activity of the venom serine proteases. These inhibitors do not affect human serine proteases as human factor Xa and thrombin, due to their selectivity.

CONCLUSION

Our study identified two small peptides able to inhibit bothropic serine proteases, but not human ones, can be used as tools to enhance knowledge of the venom composition and function. Moreover, one promising peptide (pepC) was identified that can be explored in the search for improving spp. envenomation treatment.