The overall objective of this project is to develop photosensitive compounds that can be converted to important biological molecules by irradiation with light. Analysis of cellular processes is greatly facilitated by the ability to photo-release a specific biological molecule rapidly and uniformly within a cell. Diffusional delays are overcome, permitting time-resolved measurements, and the potential exists for good spatial resolution. The emphasis will be to develop photo-release technology for biological molecules hypothesized to play a role in cell signalling. This research will involve the synthesis, photochemical characterization, and biological characterization of photolabile derivatives of inositol 1,3,4,5-tetrakisphosphates, diacylglycerols, and peptide inhibitors of calmodulin. A long-term goal is to elucidate the roles of these molecules in signal transduction cascades that control muscle contraction, although the techniques should be applicable to a wide variety of cell types. Chemical methods will also be developed for incorporation of phosphate compounds into intact cells. Used in combination, the photoactivation technique and methods for incorporation of charged compounds into intact cells will permit controlled perturbation of intracellular processes in living cells. The research will provide new insights into structure-function relationships in bio- molecules, the photochemistry of nitro-aromatic and related compounds, and ultimately, the dynamics of intracellular processes that participate in cellular signalling. %%% The overall goal of this project is to develop photosensitive compounds that can be converted to important biological molecules by irradiation with light. Analysis of cellular processes is greatly facilitated by the ability to photo-release a specific biological molecule rapidly and uniformly within a cell. The emphasis will be to develop photo-release technology for biological molecules hypothesized to play a role in cell signalling. A longer- term goal is to elucidate the roles of these molecules in signal transduction cascades that control muscle contraction, although the techniques should be applicable to a wide variety of cell types. This research will provide new insights into structure-function relationships in bio-molecules, the ultimately, into the dynamics of intracellular processes that participate in cellular signalling.
