Conotoxins Targeting Voltage-Gated Sodium Ion Channels.

Autor: Pei S; Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, China (S.P., N.W., Z.M., D.Z., X.Z., S.L.); Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou, China (D.Z., S.L.); Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Queensland, Australia (D.J.C.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M.); and George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.)., Wang N; Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, China (S.P., N.W., Z.M., D.Z., X.Z., S.L.); Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou, China (D.Z., S.L.); Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Queensland, Australia (D.J.C.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M.); and George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.)., Mei Z; Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, China (S.P., N.W., Z.M., D.Z., X.Z., S.L.); Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou, China (D.Z., S.L.); Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Queensland, Australia (D.J.C.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M.); and George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.)., Zhangsun D; Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, China (S.P., N.W., Z.M., D.Z., X.Z., S.L.); Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou, China (D.Z., S.L.); Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Queensland, Australia (D.J.C.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M.); and George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.)., Craik DJ; Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, China (S.P., N.W., Z.M., D.Z., X.Z., S.L.); Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou, China (D.Z., S.L.); Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Queensland, Australia (D.J.C.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M.); and George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.)., McIntosh JM; Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, China (S.P., N.W., Z.M., D.Z., X.Z., S.L.); Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou, China (D.Z., S.L.); Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Queensland, Australia (D.J.C.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M.); and George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.)., Zhu X; Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, China (S.P., N.W., Z.M., D.Z., X.Z., S.L.); Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou, China (D.Z., S.L.); Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Queensland, Australia (D.J.C.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M.); and George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.) zhuxiaopeng@gxu.edu.cn sulan2021@gxu.edu.cn., Luo S; Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, China (S.P., N.W., Z.M., D.Z., X.Z., S.L.); Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou, China (D.Z., S.L.); Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Queensland, Australia (D.J.C.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M.); and George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.) zhuxiaopeng@gxu.edu.cn sulan2021@gxu.edu.cn.
Jazyk: angličtina
Zdroj: Pharmacological reviews [Pharmacol Rev] 2024 Aug 15; Vol. 76 (5), pp. 828-845. Date of Electronic Publication: 2024 Aug 15.
DOI: 10.1124/pharmrev.123.000923
Abstrakt: Voltage-gated sodium (Na V ) channels are intimately involved in the generation and transmission of action potentials, and dysfunction of these channels may contribute to nervous system diseases, such as epilepsy, neuropathic pain, psychosis, autism, and cardiac arrhythmia. Many venom peptides selectively act on Na V channels. These include conotoxins, which are neurotoxins secreted by cone snails for prey capture or self-defense but which are also valuable pharmacological tools for the identification and/or treatment of human diseases. Typically, conotoxins contain two or three disulfide bonds, and these internal crossbraces contribute to conotoxins having compact, well defined structures and high stability. Of the conotoxins containing three disulfide bonds, some selectively target mammalian Na V channels and can block, stimulate, or modulate these channels. Such conotoxins have great potential to serve as pharmacological tools for studying the functions and characteristics of Na V channels or as drug leads for neurologic diseases related to Na V channels. Accordingly, discovering or designing conotoxins targeting Na V channels with high potency and selectivity is important. The amino acid sequences, disulfide bond connectivity, and three-dimensional structures are key factors that affect the biological activity of conotoxins, and targeted synthetic modifications of conotoxins can greatly improve their activity and selectivity. This review examines Na V channel-targeted conotoxins, focusing on their structures, activities, and designed modifications, with a view toward expanding their applications. SIGNIFICANCE STATEMENT: Na V channels are crucial in various neurologic diseases. Some conotoxins selectively target Na V channels, causing either blockade or activation, thus enabling their use as pharmacological tools for studying the channels' characteristics and functions. Conotoxins also have promising potential to be developed as drug leads. The disulfide bonds in these peptides are important for stabilizing their structures, thus leading to enhanced specificity and potency. Together, conotoxins targeting Na V channels have both immediate research value and promising future application prospects.
(Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)
Databáze: MEDLINE
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