Engineering of conotoxins for the treatment of pain

Carstens, Bodil B., Clark, Richard J., Daly, Norelle L., Harvey, Peta J., Kaas, Quentin and Craik, David J. (2011) Engineering of conotoxins for the treatment of pain. Current Pharmaceutical Design, 17 38: 4242-4253.

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Author Carstens, Bodil B.
Clark, Richard J.
Daly, Norelle L.
Harvey, Peta J.
Kaas, Quentin
Craik, David J.
Title Engineering of conotoxins for the treatment of pain
Journal name Current Pharmaceutical Design   Check publisher's open access policy
ISSN 1381-6128
Publication date 2011-12
Sub-type Article (original research)
Open Access Status
Volume 17
Issue 38
Start page 4242
End page 4253
Total pages 12
Place of publication Bussum, Netherlands
Publisher Bentham Science Publishers
Collection year 2012
Language eng
Abstract The peptides present in the venoms of marine snails are used by the snails to capture prey, but they have also attracted the interest of drug designers because of their potent activity against therapeutically important targets. These peptides are typically disulfiderich and target a wide range of ion channels, transporters and receptors with exquisite selectivity. In this article, we discuss structural and biological studies on several classes of conotoxins that have potential as drug leads for the treatment of pain. The chemical re-engineering of conotoxins via cyclization has been particularly valuable in improving their biopharmaceutical properties. An excellent example is the α-conotoxin Vc1.1, for which several cyclized analogs have been made. One of them was shown to be orally active in a rat pain model and this analog is currently undergoing pre-clinical development for the treatment of neuropathic pain. Several other α-conotoxins, including ImI, AuIB and MII, have proved amenable to cyclization and in all cases improvements in stability are obtained upon cyclization, suggesting that cyclization is a generally applicable approach to conotoxin stabilization. A variety of other chemical re-engineering approaches have also been used. Minor re-engineering of -conotoxin MrIa to convert its N-terminal residue to pyroglutamic acid proved particularly successful and the modified derivative, Xen2174, is currently in clinical trials for neuropathic pain.
Keyword Conotoxin
Cyclic peptides
Drug design
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
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Created: Mon, 16 Jan 2012, 14:16:13 EST by Susan Allen on behalf of Institute for Molecular Bioscience