Desenho racional de peptídeos antibacterianos análogos à toxina do escorpião Tityus sp

Abstract

The high incidence of nosocomial infection, along with the advents of bacterial resistance to multiple drugs has increased exponentially, making it necessary the search for new tools to control these pathogens. The present study focuses on the development of butylatus-1, -2 and -3, which were rationally designed based on a scorpion’s peptide from Tityus serrulatus, named TsAP-1, in order to increase the bactericidal activity with a decrease in cytotoxicity. The analogue peptides were obtained through the punctual modification of amino acid residues based in an amphipathic pattern HHh+H (h+ : positively charged hydrophilic amino acid residues; H: hydrophobic amino acid residues) found in the TsAP-1 parental peptide, thereby reducing hydrophobicity and increasing both hydrophobic moment and net charge. It was observed that the helical content also increased, promoting the increase in amphipacity of the analogue peptides Regarding their biological activities, it was observed that the parental peptide TsAP-1 did not present antibacterial activity at the maximal concentration range tested. In contrast, the analogues butylatus-1 and -2 were capable of inhibiting susceptible Escherichia coli and Enterococcus faecalis at 5.3 and 43.1 µM respectively. Interestingly, the antibacterial potential of the butylatus-3 analogue was selective to E. coli KpC, at 39.6 µM. In terms of hemolytic properties, only butylatus-2 presented cellular hemolysis at 43.1 µM. Despite the reported data on the good performance of analogues peptides, butylatus-1 stands out as an excellent candidate in the development of a new alternative against infections caused by pathogenic bacteria, due to the high action potential of at low dosages and not shown hemolysis.