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

ABSTRACT: ?-Conotoxins block voltage-gated sodium channels (VGSCs) and compete with tetrodotoxin for binding to the sodium conductance pore. Early efforts identified µ-conotoxins that preferentially blocked the skeletal muscle subtype (NaV1.4). However, the last decade witnessed a significant increase in the number of µ-conotoxins and the range of VGSC subtypes inhibited (NaV1.2, NaV1.3 or NaV1.7). Twenty µ-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 µ-conotoxins, which show promise for development of selective blockers of NaV1.2, and perhaps also NaV1.1,1.3 or 1.7.

SUBMITTER: Green BR

PROVIDER: S-EPMC4366142 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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

Green Brad R BR Bulaj Grzegorz G Norton Raymond S RS

Future medicinal chemistry 20141001 15

μ-Conotoxins block voltage-gated sodium channels (VGSCs) and compete with tetrodotoxin for binding to the sodium conductance pore. Early efforts identified µ-conotoxins that preferentially blocked the skeletal muscle subtype (NaV1.4). However, the last decade witnessed a significant increase in the number of µ-conotoxins and the range of VGSC subtypes inhibited (NaV1.2, NaV1.3 or NaV1.7). Twenty µ-conotoxin sequences have been identified to date and structure-activity relationship studies of sev ...[more]

PMID: 25406007

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Dataset Information

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

Publications

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

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