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Müller, Markus; Niemeyer, Konstantin; Urban, Nicole; Ojha, Navin K.; Zufall, Frank; Leinders-Zufall, Trese; Schäfer, Michael und Thorn-Seshold, Oliver (2022): BTDAzo: A Photoswitchable TRPC5 Channel Activator. In: Angewandte Chemie International Edition, Bd. 61, Nr. 36 [PDF, 11MB]

Abstract

Photoswitchable reagents can be powerful tools for high-precision biological control. TRPC5 is a Ca2+-permeable cation channel with distinct tissue-specific roles, from synaptic function to hormone regulation. Reagents giving spatiotemporally-resolved control over TRPC5 activity may be key to understanding and harnessing its biology. Here we develop the first photoswitchable TRPC5-modulator, BTDAzo, to address this goal. BTDAzo can photocontrol TRPC5 currents in cell culture, as well as controlling endogenous TRPC5-based neuronal Ca2+ responses in mouse brain slices. BTDAzos are also the first reported azo-benzothiadiazines, an accessible and conveniently derivatised azoheteroarene with strong two-colour photoswitching. BTDAzo ' s ability to control TRPC5 across relevant channel biology settings makes it suitable for a range of dynamically reversible photoswitching studies in TRP channel biology, with the aim to decipher the various biological roles of this centrally important ion channel.

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