Two new arthropod toxins purified from the venom of the Mexican scorpion Centruroides nigrescens

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  Two new arthropod toxins purified from the venom of the Mexican scorpion Centruroides nigrescens Abstract The venom of the slender black scorpion Centruroides nigrescens , from the State of Guerrero México, was fractionated by Sephadex G–50 gel filtration, followed by carboxymethyl cellulose ion separation and high–performance liquid chromatography, permitting to obtain two new peptides toxic to arthropods. The estimate LD 50 of the soluble venom for the insect Acheta domesticus was 11.1 μg/g body weight, and for the arthropod Armadillidium vulgare was 61.1 μg body weight . The amino acid sequence of toxin Cnige1 (toxic to A. domesticus and A. vulgare ) contains 65 amino acids, with a molecular mass of 7273.37 mass units, whereas toxin Cnige2, toxic to A. domesticus , contains 68 amino acids, with a molecular mass of 7548.81 units. Both peptides are well packed, containing 8 cysteines, which in the native venoms are forming 4 disulfide bridges each. The amino acid sequences f...

Computational engineering of the scorpion venom peptide Ttap3 enhances membrane selectivity and antimicrobial potential

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Computational engineering of the scorpion venom peptide Ttap3 enhances membrane selectivity and antimicrobial potential

Abstract

Venom-derived antimicrobial peptides (AMPs) are promising scaffolds for next-generation antimicrobial agents because of their structural diversity and membrane-targeting mechanisms. Ttap3, a peptide isolated from scorpion venom, exhibits weak antimicrobial activity despite possessing characteristic amphipathic features associated with membrane-active peptides. This study employed a computational engineering strategy to redesign Ttap3 and investigate how sequence modifications influence membrane selectivity and antimicrobial potential. Structural modelling showed that Ttap3 adopted a predominantly α-helical amphipathic conformation with moderate hydrophobic moment and relatively high hydrophobicity. Molecular dynamics simulations demonstrated preferential interaction with bacterial membrane models relative to mammalian membranes, although measurable interaction with mammalian bilayers was also observed. Rational sequence modifications involving residue substitution, sequence reversal, and modulation of amphipathicity and flexibility generated analogues with improved predicted selectivity profiles. Multi-scale molecular dynamics simulations revealed distinct membrane interaction behaviours among the redesigned analogues, including surface-associated destabilization, localized pore formation, and insertion-driven membrane perturbation. Coordinated membrane disruption involving hydrogen bond loss, lipid disorder, phospholipid deflection, altered pore radii, and increased water influx was observed predominantly in bacterial membrane systems. Partial reduction in peptide helicity during membrane interaction also appeared to contribute to selective membrane destabilization. These findings demonstrate that rational computational redesign can substantially improve the predicted antimicrobial potential and membrane selectivity of weakly active venom-derived peptides.

Owusu, S.O., Fatao, S., Laryea, M.K. et al. Computational engineering of the scorpion venom peptide Ttap3 enhances membrane selectivity and antimicrobial potential. In Silico Pharmacol. 14, 237 (2026). https://doi.org/10.1007/s40203-026-00742-0