Design and Binding Affinity of Antisense Peptides for Snake Venom Neutralization.

Abstract

Snakebites are a significant public health problem in many tropical and subtropical regions, causing extensive morbidity and mortality. Traditional snake antivenoms face multiple challenges, including allergenicity, high production costs, and logistical difficulties, highlighting the urgent need for new therapeutic approaches. This pilot study explores the potential of oligopeptides as therapeutic inhibitors targeting the neurotoxic sites of ammodytoxin A (AtxA; PDB: 3G8G) from Vipera ammodytes. We selected two sense oligopeptides to represent critical neurotoxic regions of AtxA as targets for inhibition by complementary antisense peptides. Utilizing a heuristic antisense peptide design based on the molecular recognition theory, we modeled two antisense oligopeptides as complementary counterparts for each sense oligopeptide. The modeled sense and antisense peptides were commercially synthesized, and their binding affinities were evaluated using spectrofluorometric titrations. The determined dissociation constants (K_D) were in the range of 1-10 μM for all sense-antisense pairs, revealing relatively strong binding affinities. Confirmation of sense-antisense peptide binding prompted further investigation into their potential binding to the native target protein through global docking simulations using the HPEPDOCK web server. The results highlight the applicability of molecular recognition theory in the development of antisense peptides that could change therapeutic strategies in various biomedical fields. Further studies are needed to investigate the therapeutic efficacy and broader applications of these peptides.