Merocytochalasans, Photocytochalasans and the Optical Control of the Actin Cytoskeleton

肌动蛋白细胞骨架的光松弛和肌动蛋白的光学控制 项目摘要/摘要 本项目的目标是合成和研究具有新的结构和功能特征的细胞松弛素。 松果体通常以肌动蛋白细胞骨架为靶标，并产生一些最有效的天然产物。 为人所知。这个家族的新成员将迷人的分子结构与有趣的生物活性结合在一起， 例如合并胞菌，继续出现。我们建议合成这些化合物并对其进行评估 深入研究它们对肌动蛋白细胞骨架的影响。为此，我们将开发仿生级联反应 这是基于焦没食子酸酯类化合物的氧化偶联化学。同时，我们将设计 并合成携带光开关的细胞松弛素，可以用光可逆激活。这些 “光细胞松弛剂”在辐射后改变它们的亲和力、有效性或生物利用度，并允许精确度 肌动蛋白动力学的控制。我们将把我们的肌动蛋白细胞骨架光学控制计划扩展到 茉莉花内酯的光开关衍生物。为了支持我们的主张，我们提供了以下初步结果 证明肌动蛋白细胞骨架的光药理学确实是可行的。

Merocytochalasans, Photocytochalasans, and the Optical Control of the Actin Cytoskeleton Project Summary/Abstract The goal of this project is to synthesize and study cytochalasans with new structural and functional features. Cytochalasans generally target the actin cytoskeleton and account for some of the most potent natural products known. New members of this family that combine fascinating molecular structures with interesting bioactivities, such as the merocytochalasans, continue to emerge. We propose to synthesize these compounds and evaluate them in depth for their effect on the actin cytoskeleton. To this end, we will develop biomimetic cascade reactions that are based on the largely unexplored oxidative coupling chemistry of pyrogallols. In parallel, we will design and synthesize cytochalasans that bear photoswitches and can be reversibly activated with light. These “photocytochalasans” change their affinity, efficacy, or bioavailability upon irradiation and allow for the precision control of actin dynamics. We will extend our program on the optical control of the actin cytoskeleton to photoswitchable derivatives of the jasplakinolides. To support our claims, we provide preliminary results that demonstrate that the photopharmacology of the actin cytoskeleton is indeed viable.