Photoactivatable and photolabile pharmacophores: lessons learned from capsaicin

光活化和光不稳定药效团:从辣椒素中汲取的经验教训

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Abstract

Light-controlled molecules have become valuable tools for studying biological systems offering an unparalleled control in space and time. Specifically, the remote-controllable (de)activation of small molecules is attractive both to study molecular processes from a fundamental point of view and to develop future precision therapeutics. While pronounced changes through light-induced cleavage of photolabile protecting groups and the accompanying liberation of bioactive small molecules have become a highly successful strategy, approaches that focus solely on the revert process, i.e. the photochemical deactivation of bioactive agents, are sparse. In this work, we studied whether a given bioactive compound could be made photolability by structural design. We thus used the example of capsaicinoids, which control the transient receptor potential cation channel subfamily V member 1 (TRPV1), to generate both suitable light activation and deactivation strategies.

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