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Merocytochalasans, Photocytochalasans and the Optical Control of the Actin Cytoskeleton

细胞松弛素、光细胞松弛素和肌动蛋白细胞骨架的光学控制

基本信息

批准号：
9752602
负责人：
DIRK HARTWIG TRAUNER
金额：
$ 26.6万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2022-04-30
项目状态：
已结题

项目摘要

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.

部分细胞松弛素、光细胞松弛素和肌动蛋白细胞骨架的光学控制项目总结/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。细胞松弛素通常靶向肌动蛋白细胞骨架，并解释了一些最有效的天然产物知道的这个家族的新成员将联合收割机迷人的分子结构与有趣的生物活性结合在一起，如裂细胞松弛菌继续出现。我们建议合成这些化合物并评价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它们基于焦性没食子酚的大量未开发的氧化偶联化学。与此同时，我们将设计并合成带有光开关并可被光可逆激活的细胞松弛素。这些 “光细胞松弛素”在照射后改变它们的亲和力、功效或生物利用度，并允许精确地调节它们的生物利用度。肌动蛋白动力学的控制。我们将扩大我们的计划对光学控制的肌动蛋白细胞骨架，茉莉内酯的可光转换衍生物。为了支持我们的主张，我们提供了初步结果，证明了肌动蛋白细胞骨架的药理学确实是可行的。