# Photoactivatable and photolabile pharmacophores: lessons learned from capsaicin

## TL;DR

This paper explores how light can be used to control the activity of a compound that affects a specific cell channel, using capsaicin as an example.

## Contribution

The study introduces a new approach to design photolabile compounds that can be activated and deactivated using light.

## Key findings

- Photolabile chromopharmacophores based on capsaicinoids can activate the TRPV1 channel.
- Photoproducts of these compounds do not activate the TRPV1 channel.
- Structural design allows for light-controlled activation and deactivation of bioactive molecules.

## 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.

Structurally merging light-susceptible with bioactive molecules allows to generate photolabile chromopharmacophores. Using capsaicinoids, chromopharmacophores could activate the TRPV1 channel, while no activation is observed for the photoproducts.