Analogs of the Scorpion Venom Peptide Stigmurin: Structural Assessment, Toxicity, and Increased Antimicrobial Activity

Abstract

Scorpion venom is a rich source of biologically active components and various peptides with high-potential therapeutic use that have been characterized for their antimicrobial and antiproliferative activities. Stigmurin is a peptide identified from the Tityus stigmurus venom gland with high antibacterial and antiproliferative activities and low toxicity. Amino acid substitutions in peptides without a disulfide bridge sequence have been made with the aim of reducing their toxicity and increasing their biological activities. The purpose of this study was to evaluate the structural conformation and structural stability, as well as antimicrobial, antiproliferative, and hemolytic activities of two peptide analogs to Stigmurin, denominated StigA6 and StigA16. In silico analysis revealed the α-helix structure for both analog peptides, which was confirmed by circular dichroism. Data showed that the net charge and hydrophobic moment of the analog peptides were higher than those for Stigmurin, which can explain the increase in antimicrobial activity presented by them. Both analog peptides exhibited activity on cancerous cells similar to the native peptide; however, they were less toxic when tested on the normal cell line. These results reveal a potential biotechnological application of the analog peptides StigA6 and StigA16 as prototypes to new therapeutic agents.

Potent and Broad-Spectrum Antimicrobial Activity of Analogs from the Scorpion Peptide Stigmurin

“…Various antimicrobial peptides from aquatic animals have been isolated and tested against epimatigote forms of T. cruzi ; however, they did not show antiparasitic activity for these strains [28], different from the analog peptides StigA25 and StigA31, which demonstrated a high inhibition rate. Similar activity was also shown for other analog peptides from the scorpion peptide Stigmurin [15] and various analog peptides from scorpion venom with significant activity against trypanosomatides [29]. When tested in trypomastigote forms of the T. cruzi and Y strains we observed the same pattern for epimastigote, with the analogs peptides showing higher activity than the native peptide Stigmurin.…”

“…Regarding the antiparasitic activity, the three tested peptides inhibited the epimastigote forms of the T. cruzi Y strain. No significant difference was observed between the inhibition caused by the analog peptides; though when compared with the native peptide Stigmurin in an earlier study, both analog peptides showed higher antiparasitic activity [15]. Various antimicrobial peptides from aquatic animals have been isolated and tested against epimatigote forms of T. cruzi ; however, they did not show antiparasitic activity for these strains [28], different from the analog peptides StigA25 and StigA31, which demonstrated a high inhibition rate.…”

“…Amino acid substitutions in a short peptide chain have been reported to improve the native peptide characteristics, increasing its biological activity and reducing its toxicity. This is a promising approach to develop new molecules with therapeutic potential [15]. To design the analogs of this study, we replaced the polar and uncharged Ser and Gly residues of the native peptide with positively charged Lys residues in order to increase the positive charge of Stigmurin and observe the effect of increasing the charge on antimicrobial activity and hemolytic activity of this non-hemolytic peptide with a low positive charge (+2).…”

Variable Surface Glycoprotein from Trypanosoma brucei Undergoes Cleavage by Matrix Metalloproteinases: An in silico Approach

“…Our recent studies focus on the evaluation of potential new drugs in the context of trypanosomatid infections. Thus, the mechanism of the antigenic variation of T. brucei seems to be an interesting target for the search for potential new antiparasitic molecules [43,44]. Consequently, understanding the mechanism of VSG release and all the involved molecules represents an important strategy for the development of new drugs against infections caused by T. brucei.…”

Antimicrobials from Venomous Animals: An Overview

“…The increase in the net positive charge of these analogues facilitates their interaction with the target cell membranes [43]. Two analogs of the peptide stigmurin from the Tityus stigmurus venom gland named StigA6 and StigA16 revealed increased antimicrobial activity and less toxicity on the normal cell line, while retaining the activity of the native peptide on cancer cells [44].…”