Structure and function of mu-conotoxins, peptide-based sodium channel blockers with analgesic activity

Brad Reed Green, Grzegorz Bulaj, Raymond Stanley Norton

Research output: Contribution to journalArticleResearchpeer-review

27 Citations (Scopus)

Abstract

?-Conotoxins block voltage-gated sodium channels (VGSCs) and compete with tetrodotoxin for binding to the sodium conductance pore. Early efforts identified ?-conotoxins that preferentially blocked the skeletal muscle subtype (NaV1.4). However, the last decade witnessed a significant increase in the number of ?-conotoxins and the range of VGSC subtypes inhibited (NaV1.2, NaV1.3 or NaV1.7). Twenty ?-conotoxin sequences have been identified to date and structure-activity relationship studies of several of these identified key residues responsible for interactions with VGSC subtypes. Efforts to engineer-in subtype specificity are driven by in vivo analgesic and neuromuscular blocking activities. This review summarizes structural and pharmacological studies of ?-conotoxins, which show promise for development of selective blockers of NaV1.2, and perhaps also NaV1.1,1.3 or 1.7.
Original languageEnglish
Pages (from-to)1677 - 1698
Number of pages22
JournalFuture Medicinal Chemistry
Volume6
Issue number15
DOIs
Publication statusPublished - 2014

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