Photo‐Controlled Release of Small Signaling Molecules to Induce Biological Responses

Chemical modifications of proteins or cofactors, including acetylation and oxidation of amino acid residues of various signal proteins, whether transient or successive, play key roles in modulating biological functions. Small molecules that have signaling functions in biological systems through the chemical modification of proteins include nitric oxide (NO), hydrogen peroxide, carbon monoxide, and hydrogen sulfide. To investigate the pathophysiological roles of these molecules, caged compounds have been developed that allow precise spatiotemporal control of the release of these species in response to photoirradiation in the ultraviolet or visible region. For example, photocontrollable NO releasers can regulate the responses of blood vessels in vivo and ex vivo. In addition, photocontrollable (caged) inhibitors of histone deacetylase (HDAC) can be used to regulate HDAC activity in response to photoirradiation. Such photocontrol technology has provided chemical tools for a variety of biological studies, including investigations of epigenetic mechanisms. Spatiotemporally controlled release of small signaling molecules from caged compounds in response to photo‐irradiation is useful for studying the dynamics of various biological phenomena, including epigenetic modifications and oxidation. Caged compounds for delivery of nitric oxide, hydrogen sulfide, reactive oxygen species, and histone deacetylase inhibitor are reviewed and discussed.