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Mu-conotoxins as leads in the development of new analgesics.

ABSTRACT: Voltage-gated sodium channels (VGSCs) contain a specific binding site for a family of cone shell toxins known as mu-conotoxins. As some VGSCs are involved in pain perception and mu-conotoxins are able to block these channels, mu-conotoxins show considerable potential as analgesics. Recent studies have advanced our understanding of the three-dimensional structures and structure-function relationships of the mu-conotoxins, including their interaction with VGSCs. Truncated peptide analogues of the native toxins have been created in which secondary structure elements are stabilized by non-native linkers such as lactam bridges. Ultimately, it would be desirable to capture the favourable analgesic properties of the native toxins, in particular their potency and channel sub-type selectivity, in non-peptide mimetics. Such mimetics would constitute lead compounds in the development of new therapeutics for the treatment of pain.

SUBMITTER: Norton RS

PROVIDER: S-EPMC6257286 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Mu-conotoxins as leads in the development of new analgesics.

Norton Raymond S RS

Molecules (Basel, Switzerland) 20100419 4

Voltage-gated sodium channels (VGSCs) contain a specific binding site for a family of cone shell toxins known as mu-conotoxins. As some VGSCs are involved in pain perception and mu-conotoxins are able to block these channels, mu-conotoxins show considerable potential as analgesics. Recent studies have advanced our understanding of the three-dimensional structures and structure-function relationships of the mu-conotoxins, including their interaction with VGSCs. Truncated peptide analogues of the ...[more]

PMID: 20428082

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