CAGED PROBES FOR CELLULAR PHYSIOLOGY

该项目的目标是开发一个广泛的 优化的光敏探针（笼状化合物）， 生理学家利用光来操纵和控制动态信号 活细胞中的过程。 具体而言，该提案有五个主要重点：1）开发新的笼 组，以实现高产品收率，高光释放速度和高 光解前稳定性 2)合成笼状探针，用于操作 细胞内Ca2+动态 具体目标是笼状钙和 一种笼状抗钙剂，用于解决细胞内的问题， 生理学和兰尼碱受体的笼状激动剂。 3)发展 新的笼状神经递质，优化为低预光解 激动剂活性和非常快的光释放动力学。 4)开发一个 制备笼状肽以允许光活化和光活化的方法 抑制细胞内酶活性。 5)的应用 新创建的光化学工具，以四个具体的问题，在三个 细胞生理学领域;心脏兴奋-收缩偶联 细胞、感觉神经元兴奋性的调节和整合 神经元树突的突触输入。

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.