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Development of photoactivatable drugs enables nicotinic optopharmacology

By Sambashiva Banala, Matthew C. Arvin, Nicolas M. Bannon, Xiao-Tao Jin, Yong Wang, Guiqing Zhao, John J. Marshall, Kyle R. Gee, David L. Wokosin, Anis Contractor, Henry A. Lester, Yevgenia Kozorovitskiy, Ryan M. Drenan, Luke Lavis

Posted 05 Feb 2018
bioRxiv DOI: 10.1101/260232

Photoactivatable ('caged') pharmacological agents have revolutionized neuroscience but the palette of available ligands is limited. We describe a general method for caging tertiary amines using an unconventional quaternary ammonium linkage that is chemically stable and elicits a desirable red-shift in activation wavelength. A photoactivatable nicotine (PA-Nic) prepared using this strategy could be uncaged via 1- or 2-photon excitation, making it useful for optopharmacology experiments to study nicotinic acetylcholine receptors (nAChRs) in different experimental preparations and spatiotemporal scales.

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