CAGED PROBES FOR CELLULAR PHYSIOLOGY

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The objective of this project is to develop a broad spectrum of optimized photosensitive probes (caged compounds) to allow cellular physiologists to use light to manipulate and control dynamic signaling processes in living cells. Specifically, the proposal has five major foci: 1) Develop new caging groups to achieve high product yield, high photorelease speed and high prephotolysis stability. 2) Synthesize caged probes for manipulating intracellular Ca2+ dynamics. Specific targets are a caged calcium and a caged anti-calcium optimized to address problems in cellular physiology, and a caged agonist for the ryanodine receptor. 3) Develop new caged neurotransmitters that are optimized for low prephotolysis agonist activity and very fast photorelease kinetics. 4) Develop a method for making caged peptides to allow photo-activation and photo- inhibition of intracellular enzyme activities. 5) Application of the newly created photochemical tools to four specific problems in three areas of cellular physiology; excitation-contraction coupling in cardiac cells, regulation of excitability in sensory neurons, and integration of synaptic inputs by neuronal dendrites.