Peptídeos aniônicos presentes na peçonha do escorpião Tityus stigmurus: avaliação estrutural e atividade biológica

Abstract

Scorpion venoms are a rich source of peptides, which may be classified as disulfide-bridged or non-disulfide-bridged peptides. Among them, there are anionic peptides, rich in aspartic and glutamic acid residues. Despite being the most abundant component in the venom gland of Tityus stigmurus (the prevalent scorpion species in Northeast Brazil), they are poorly characterized in the literature. This work presents, for the first time, structural characterization and biological activity assays of an anionic peptide from the venom of the scorpion T. stigmurus, named TanP. The three-dimensional structure of TanP was obtained by computational modeling and refined by molecular dynamic (MD) simulations. Furthermore, we have performed circular dichroism (CD) analysis to predict TanP secondary structure, and UV-visible spectroscopy to evaluate its chelating activity. CD indicated predominance of random coil conformation in aqueous medium, as well as changes in structure depending on pH and temperature. TanP has chelating activity on copper ions, which modified the peptide’s secondary structure. These results were corroborated by MD data. The molar ratio of binding (TanP:copper) depends on the concentration of peptide. TanP was not cytotoxic to normal or cancer cell lines, and showed an ability to inhibit the in vitro release of nitric oxide by LPS-stimulated macrophages. In this way, the results suggest TanP is a promising peptide for therapeutic application as a chelating, immunomodulatory and antioxidant agent.