Conus venom peptide pharmacology

Lewis, Richard J., Dutertre, Sebastien, Vetter, Irina and Christie, MacDonald J. (2012) Conus venom peptide pharmacology. Pharmacological Reviews, 64 2: 259-298. doi:10.1124/pr.111.005322

Author Lewis, Richard J.
Dutertre, Sebastien
Vetter, Irina
Christie, MacDonald J.
Title Conus venom peptide pharmacology
Journal name Pharmacological Reviews   Check publisher's open access policy
ISSN 0031-6997
Publication date 2012-04-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1124/pr.111.005322
Volume 64
Issue 2
Start page 259
End page 298
Total pages 40
Place of publication Bethesda, MD, United States
Publisher American Society for Pharmacology and Experimental Therapeutics
Language eng
Formatted abstract
Conopeptides are a diverse group of recently evolved venom peptides used for prey capture and/or defense. Each species of cone snails produces in excess of 1000 conopeptides, with those pharmacologically characterized (∼0.1%) targeting a diverse range of membrane proteins typically with high potency and specificity. The majority of conopeptides inhibit voltage- or ligand-gated ion channels, providing valuable research tools for the dissection of the role played by specific ion channels in excitable cells. It is noteworthy that many of these targets are found to be expressed in pain pathways, with several conopeptides having entered the clinic as potential treatments for pain [e.g., pyroglutamate1-MrIA (Xen2174)] and one now marketed for intrathecal treatment of severe pain [ziconotide (Prialt)]. This review discusses the diversity, pharmacology, structure-activity relationships, and therapeutic potential of cone snail venom peptide families acting at voltage-gated ion channels (ω-, μ-, μO-, δ-, ι-, and κ-conotoxins), ligand-gated ion channels (α-conotoxins, σ-conotoxin, ikot-ikot, and conantokins), G-protein-coupled receptors (ρ-conopeptides, conopressins, and contulakins), and neurotransmitter transporters (χ-conopeptides), with expanded discussion on the clinical potential of sodium and calcium channel inhibitors and α-conotoxins. Expanding the discovery of new bioactives using proteomic/transcriptomic approaches combined with high-throughput platforms and better defining conopeptide structure-activity relationships using relevant membrane protein crystal structures are expected to grow the already significant impact conopeptides have had as both research probes and leads to new therapies.
Keyword Nicotinic acetylcholine-receptors
Voltage-gated sodium
Sensitive calcium-channel
Omega-conotoxin gvia
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
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