Photoactivatable and Photolabile Pharmacophores: Lessons Learned from Capsaicin

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 to both 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 has 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 photolability can be designed into a given bioactive compound on the example of capsaicinoids controlling the transient receptor potential cation channel subfamily V member 1 (TRPV1) including both on light activation and deactivation strategies.