Development and application of fluorescent, green light-activatable caged compound

Caged compound is one of the most powerful tools for spatiotemporal control of biomolecules in cells, which can be activated by irradiation of light. However, ultra violet light, which is required for activation of caged compounds, can damage cells and has poor permeability into tissues. In addition, invisibility of caged compounds makes it difficult to tell distribution of released small molecules. At the conference, we will describe the development of novel caging group and new caged compounds which are fluorescently visible and efficiently activatable with green light. We have found that boron dipyrromethene (BODIPY), known as a widely used fluorophore, is a potential caging group for phenol, carboxyl acid and amine, which can be photolized with irradiation of green light at around 500 nm wavelength. Based on the novel photo-reaction of 4-phenoxy BODIPY derivatives, we have developed caged histamine and applied it to HeLa cells. Photo-irradiation to cells in the presence of caged histamine induced transient increase of calcium ion in cytosol, which was specifically inhibited with pyrilamine, a H1 blocker. Also, we showed that BODIPY-caged compound can be utilized in vivo with tissue-permeable 500 nm green light.