Development of photoactivatable drugs enables nicotinic optopharmacology

Banala, S.; Arvin, M. C.; Bannon, N. M.; Jin, X.-T.; Wang, Y.; Zhao, G.; Marshall, J. J.; Gee, K. R.; Wokosin, D. L.; Contractor, A.; Henry, L. A.; Kozorovitskiy, Y.; Drenan, R. M.; Lavis, L. D.

doi:10.1101/260232

bioRxiv · 10.1101/260232

Development of photoactivatable drugs enables nicotinic optopharmacology

Banala, S.·Arvin, M. C.·Bannon, N. M.·Jin, X.-T.·Wang, Y.·Zhao, G.·Marshall, J. J.·Gee, K. R.·Wokosin, D. L.·Contractor, A.·Henry, L. A.·Kozorovitskiy, Y.·Drenan, R. M.·Lavis, L. D.

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Abstract

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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Banala, S., Arvin, M. C., Bannon, N. M., Jin, X.-T., Wang, Y., Zhao, G., Marshall, J. J., Gee, K. R., Wokosin, D. L., Contractor, A., Henry, L. A., Kozorovitskiy, Y., Drenan, R. M., Lavis, L. D.. 2018-02-05. Development of photoactivatable drugs enables nicotinic optopharmacology. https://doi.org/10.1101/260232

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