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Cloning, synthesis, and characterization of αO-conotoxin GeXIVA, a potent α9α10 nicotinic acetylcholine receptor antagonist

Luo, Sulan, Zhangsun, Dongting, Harvey, Peta J., Kaas, Quentin, Wu, Yong, Zhu, Xiaopeng, Hu, Yuanyan, Li, Xiaodan, Tsetlin, Victor I., Christensen, Sean, Romero, Haylie K., McIntyre, Melissa, Dowell, Cheryl, Baxter, James C., Elmslie, Keith S., Craik, David J., McIntosh, J. Michael
Proceedings of the National Academy of Sciences of the United States of America 2015 v.112 no.30 pp. E4026
analgesics, antagonists, breast neoplasms, cholinergic receptors, medicinal properties, pain, peptides
The α9α10 nicotinic AChR (nAChR) subtype is a recently identified target for the development of breast cancer chemotherapeutics and analgesics, particularly to treat neuropathic pain. Structure/function analyses of antagonists of this subtype are therefore essential for the development of specific therapeutic compounds. The Conus genus is a rich source of pharmacologically active peptides, and we report here that the αO-conotoxin GeXIVA is a potent and selective antagonist of the α9α10 nAChR subtype. GeXIVA displays unique structural properties among other Conus peptides and represents a previously unidentified template for molecules active against neuropathic pain.