decaging

Decaging refers to the removal of a protective cage or cap from a molecule, typically to restore its native functional group or biological activity. In chemical biology, caged compounds consist of an active molecule rendered inactive by a chemical group that blocks a reactive site. Decaging is the process by which the cage is removed, often triggering the molecule's activity. The term is commonly used in conjunction with photolabile cages, where light exposure cleaves the cage, and with chemically labile cages that are removed by specific reagents or conditions.

Common decaging approaches include photolysis of photolabile protecting groups such as nitrobenzyl- or coumarin-based cages; upon irradiation with UV or visible light, the protecting group fragments, releasing the active molecule. Other strategies rely on chemical decaging via hydrolysis, reduction, or oxidation, or enzymatic cleavage of the cage.

Applications of decaging span several fields. In neuroscience and cell biology, decaging enables spatiotemporal control of neurotransmitters, calcium indicators, or signaling molecules. In drug delivery and photopharmacology, decaging allows on-demand drug activation. In materials science, decaging can trigger changes in polymer properties or biointerfaces.

Limitations and challenges include light penetration limits in biological tissue, potential phototoxicity and toxic byproducts from cage photolysis, incomplete decaging or leakage of activity, the need for cage orthogonality to avoid off-target activation, and the stability of cages under physiological conditions.