Poor drug selectivity can result in off-target effects, toxicity, and an incomplete understanding of drug mechanisms. Photopharmacology addresses these challenges by using light as an external trigger to modulate drug activity, enabling precise control over drug dosing. Photocages, also known as labile protecting groups, allow spatiotemporal regulation of the release of bioactive molecules in living systems.1,2
This project focuses on the development of a modular platform for organelle-targeting caging groups that utilise visible light to trigger the photo-release of the bioactive of interest. The photocage design is based on a fluorescent coumarin scaffold, which enables monitoring of the subcellular localisation of the caged compound prior to photoactivation. Upon light irradiation, the release of the bioactive payload is accompanied by a change in fluorescence, allowing us to monitor the uncaging process.
Importantly, a click handle is retained on the photocage scaffold, enabling late-stage conjugation of diverse organelle-targeting ligands. This strategy facilitates rapid installation and parallel evaluation of different targeting groups, enhancing modularity and synthetic efficiency. Together, these features provide a general platform to study the effects of controlled subcellular localisation and light-triggered release of bioactive molecules, enabling superior spatiotemporal control compared to conventional drug dosing approaches.