Senecioylcholine in Heterometrus spinifer scorpion venom activates vertebrate nicotinic acetylcholine receptors

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  Senecioylcholine in Heterometrus spinifer scorpion venom activates vertebrate nicotinic acetylcholine receptors Abstract Introduction: Scorpion venoms are natural sources of neurotoxins that primarily modulate the properties of neuronal ion channels, particularly voltage-gated sodium and potassium channels. However, they also contain a variety of small bioactive molecules that have been largely neglected in the omics era of toxinological research. Methods: In the present study, we employed a high-throughput FLIPR screen of arthropod venoms against nicotinic acetylcholine receptors (nAChRs) expressed in the human SH-SY5Y neuroblastoma cell line. Results: The venom of the Malaysian forest scorpion Heterometrus spinifer (family: Scorpionidae) proved to be an agonist of nAChRs, and the small choline ester senecioylcholine was identified as being responsible for the observed effect. Synthetic senecioylcholine and its isomers tigloylcholine and angeloylcholine were not insecticidal wh...

Design of antinociceptive peptide by grafting domains between scorpion β-neurotoxins

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Design of antinociceptive peptide by grafting domains between scorpion β-neurotoxins

Abstract

Neurotoxic peptides from venomous animals have been pointed out as antinociceptive therapeutic leads. Venom peptides have modulation properties on isoforms of voltage-gated sodium channels (VGSC), associated with pathologies such as neuropathic or inflammatory pain. The β-neurotoxins obtained from scorpion venoms are peptides that can alter the kinetics of VGSC by binding to its receptor site 4. CeII8 is a non-lethal scorpion β-neurotoxin that has been reported to interact with hNaV1.7, a VGSC isoform related to the codification and processing of painful stimulus (nociception), and it is involved in pain pathologies. On the other hand, CssII is a lethal scorpion β-neurotoxin that binds mainly to site 4 of hNav1.6. Because of this, we used computational methods and the amino acid sequence of the novo recombinant neurotoxin rCssII-RCR to graft in some of its domains existing amino acids from the non-lethal CeII8 to generate a chimeric peptide with antinociceptive activity, named rCssII-Del-D23A-TCD. This peptide variant was found to have antinociceptive activity in inflammatory and neuropathic pain models with an effect comparable to the mu-opioid receptor agonists DAMGO (H-Tyr-D-Ala-Gly-N(Me) Phe-Gly-ol).
Montero-Dominguez, P. A., Restano-Cassulini, R., Magaña-Ávila, L. C., Almanza, A., Mercado, F., & Corzo, G. (2025). Design of antinociceptive peptide by grafting domains between scorpion β-neurotoxins. Bioorganic Chemistry, 162, 108592. https://doi.org/10.1016/j.bioorg.2025.108592