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Title: Chemical tools for controlling cellular response: caged NO and caged HDAC inhibitor
Nitric oxide (NO) is now recognized as a physiological cellular second messenger molecule playing various important physiological roles, and as one of the gaseous mediators due to its gaseous nature under ambient conditions, as well as H2S and CO. To investigate biological functions of gaseous mediators would be very interesting because it may reveal new mechanisms of our body functions or lead to profound understanding on physiology of our body. However, it is in general hard to use gaseous mediators in biological experiments directly because of their unstable and relatively reactive nature. To overcome this difficulty, it is very helpful to use chemical donors of these gaseous mediators, which are chemicals releasing a specific gaseous mediator in biological experimental systems such as buffers and culture media. Especially, photocontrollable chemical donors, or caged compounds, are advantageous because the release of the mediators can be controllable by photoirradiation so that the site and timing can be controlled on demand and mimic physiological action of gaseous mediator release. We have recently developed unique caged NOs by adopting photoisomerization reaction of nitrobenzene or photoinduced redox reaction of N-nitrosoaminophenol. Our caged NOs were found to release NO in response to UVA or visible light. Some of them are applicable to cell culture. By utilizing near infrared (NIR) femtosecond pulse laser, one of our caged NO was found to induce tissue response related to NO in vivo .
HDAC is one of the key enzymes for epigenetic control of cellular responses especially related proliferation of cancer cells and stem cells. We have been investigating caged HDAC inhibitors. Our coumarin-caged SAHA was found to inhibit HDAC activity in vitro and in cells in response to photoirradiation. It is expected to be applicable for spatiotemporal control of cellular differentiation in cancer cells or stem cells.