CAGED PROBES FOR CELLULAR PHYSIOLOGY

该项目的目标是开发广泛的 优化的光敏探针(笼状化合物)允许细胞 生理学家利用光来操纵和控制动态信号 活细胞中的过程。 具体地说，该提案有五大重点：1)开发新的网箱 集团实现了高产品收率、高光解速度和高 光解前稳定性。2)合成用于操作的笼式探头 细胞内钙动态变化。具体目标是笼子里的钙和 一种针对细胞内问题而优化的笼式抗钙剂 生理学，和笼子里兰尼定受体激动剂。3)发展 新型笼式神经递质，专为低光前分解而优化 激动剂活性和非常快的光释放动力学。4)制定 一种笼状肽的制造方法，以允许光活化和光敏 抑制细胞内酶活性。5)适用于 新创建的光化学工具解决三个具体问题中的四个 细胞生理学领域；心脏的兴奋-收缩耦合 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.