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Molecules 2010, 15(4), 2825-2844;

µ-Conotoxins as Leads in the Development of New Analgesics

Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia
Received: 9 March 2010 / Revised: 6 April 2010 / Accepted: 12 April 2010 / Published: 19 April 2010
(This article belongs to the Special Issue Toxins - Organic and Analytical Chemistry)
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Voltage-gated sodium channels (VGSCs) contain a specific binding site for a family of cone shell toxins known as µ-conotoxins. As some VGSCs are involved in pain perception and µ-conotoxins are able to block these channels, µ-conotoxins show considerable potential as analgesics. Recent studies have advanced our understanding of the three-dimensional structures and structure-function relationships of the µ-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. View Full-Text
Keywords: cone shell; toxin; sodium channel; pain; peptide mimetic cone shell; toxin; sodium channel; pain; peptide mimetic

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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Norton, R.S. µ-Conotoxins as Leads in the Development of New Analgesics. Molecules 2010, 15, 2825-2844.

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