Dicarba Analogues of α-Conotoxin RgIA. Structure, Stability and Activity at Potential Pain Targets

Authors Sandeep Chhabra, Alessia Belgi, Peter Bartels, Bianca van Lierop, Samuel D. Robinson, Shiva N. Kompella, Andrew Hung, Brid P. Callaghan, David J. Adams, Andrea J. Robinson and Raymond S. Norton
Published Journal of Medicinal Chemistry
Graphical abstract  Rg1A
Abstract α-Conotoxin RgIA is an antagonist of the α9α10 nicotinic acetylcholine receptor (nAChR) subtype and inhibits high voltage-activated N-type calcium channels. RgIA has therapeutic potential for the treatment of pain but reduction of the disulfide bond framework under physiological conditions represents a potential liability for clinical applications. We synthesized four RgIA analogues that replaced native disulfide pairs with non-reducible dicarba bridges. The analogues also exhibited superior stability over native peptide.
Citation S. Chhabra, A. Belgi, P. Bartels, B. van Lierop, S. D. Robinson, S. N. Kompella, A. Hung, B. P. Callaghan, D. J. Adams, A. J. Robinson and R. S. Norton, J. Med. Chem, 2014, 57(23), 9933-9944
Pdf
Doi 10.1021/jm501126u.
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This entry was posted in Conotoxins, Metathesis, Publications, Publications 2014. Bookmark the permalink.

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