Conus victoriae cone snails catch food by injecting a potent venom that renders prey paralyzed.

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Venom produced by the cone snail, Conus victoriae, contain proteins that induce paralysis in prey. The conotoxin is more than two orders of magnitude more potent than the current leading drug for neuropathic pain. These toxins can be models for use as analgesics for treating neuropathic pain in humans at lower concentrations. Conventional analgesics have many downsides including their gradual loss of effectiveness, their potential for creating addiction and abuse, and their harmful side effects.

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"[T]he synthetic cyclization of a model conotoxin, MII, stabilized the structure and reduced susceptibility to proteolysis, thus potentially enhancing the therapeutic potential of conotoxins…we applied this approach to re-engineer the a-conotoxin Vc1.1, from the cone snail Conus victoriae, and demonstrate that the cyclic peptide is orally active...It is an effective analgesic in several rat models of neuropathic pain and therefore has attracted considerable interest as a potential treatment for this condition." (Clark 2010:6545)

"Our orally active peptide exhibits higher selectivity and potency for GABA B receptor- mediated N-type Ca2+ channel currents, the proposed target for analgesia, than the parent linear peptide...By developing an orally active analogue of Vc1.1, we have substantially enhanced its potential as a new therapy for neuropathic pain. More generally, the high potency and selectivity of peptides and their applicability to an enormous range of medical conditions make them attractive leads for drug development. However, for their potential to be fully realized, approaches for improving their pharmaceutical properties, including improved stability and oral activity, must be developed. In this study, we have demonstrated that backbone cyclization can be used to achieve this goal." (Clark 2010:6547)

Journal article
The Engineering of an Orally Active Conotoxin for the Treatment of Neuropathic PainAngewandte ChemieJune 8, 2010
Richard J. Clark, Jonas Jensen, Simon T. Nevin, Brid P. Callaghan, David J. Adams, David J. Craik

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Living System/s

Organism
Cloth-of-Gold ConeConusSpecies

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