Mu-conotoxins as leads in the development of new analgesics.
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.
Norton
Raymond S
RS
Walter and Eliza Hall Institute of Medical Research, Victoria, Australia. ray.norton@wehi.edu.au
D000700:Analgesics / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D020916:Conotoxins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy; D017433:Protein Structure, Secondary; D015222:Sodium Channels / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000700:Analgesics; D020916:Conotoxins; D015222:Sodium Channels