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Optical Control of the Actin Cytoskeleton

肌动蛋白细胞骨架的光学控制

基本信息

批准号：
10736022
负责人：
DIRK HARTWIG TRAUNER
金额：
$ 32.72万
依托单位：
UNIVERSITY OF PENNSYLVANIA
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 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10736022
关键词：
Actins Alkynes Allosteric Site Azides Binding Biological Cancer cell line Cardiac Cell physiology Cells Cellular biology Chemicals Clinical Collaborations Communities Complex Cryoelectron Microscopy Cytochalasin D Cytochalasins Cytoskeleton Darkness Development Docking Drug Targeting Elongation Factor F-Actin Filament G Actin Glues Goals Grant Halogens Hela Cells Human Label Length Light Location Marine Toxins Microglia Molecular Molecular Motors Motor Myosin S-2 Myosin Type II Natural Products Neoplasm Metastasis Neurons Oligodendroglia Optics Organelles Parents Pathway interactions Play Polymers Porifera Property Proteins Roentgen Rays Role Running Structural Biologist Structure Structure-Activity Relationship Therapeutic Toxin Tubulin Visible Radiation X-Ray Crystallography Yeasts analog azobenzene blebbistatin cell motility cost cytotoxic design high throughput screening improved in silico inhibitor jasplakinolide latrunculin A latrunculin B monomer pharmacokinetics and pharmacodynamics programs rational design redshift small molecule stem structural biology temporal measurement tool vasodilator-stimulated phosphoprotein

项目摘要

Project Summary/Abstract The goal of this project is the optical control of the actin cytoskeleton with photoswitchable molecules. These compounds target monomeric G-actin, polymeric F-actin, the nucleator complex Arp2/3, and the motor protein myosin II. Our probes aimed at F-actin and G-actin are derived from the natural products jasplakinolide, yielding opto-Jasp, cytochalasin D (opto-Chal), and latrunculin B (opto-Lat), respectively. The photoswitchable molecules for Arp2/3 stem from CK-666 (opto-CK) and the photoswitchable myosin 2 inhibitors from blebbistatin and similar compounds (opto-MI). We have already obtained significant preliminary results in a variety of cells (e.g. yeast, HeLa, neurons, oligodendrocytes, microglia). Our proposed program constitutes the continuation of our long-standing and successful program on optically controlling actin and tubulin, as well as associated motor proteins with photoswitchable small molecules. The close collaboration between a chemical biologist and a structural biologist will yield useful probes that are shared with the community and could form the basis of a new form of precision chemotherapeutics.

项目总结/文摘

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Computational Exploration of the Mechanism of Critical Steps in the Biomimetic Synthesis of Preuisolactone A, and Discovery of New Ambimodal (5 + 2)/(4 + 2) Cycloadditions.

DOI：
10.1021/jacs.1c01856
发表时间：
2021-04
期刊：
Journal of the American Chemical Society
影响因子：
15
作者：
Hong Zhang;Alexander J. E. Novak;Cooper S. Jamieson;Xiao-song Xue;Shuming Chen;D. Trauner;K. Houk
通讯作者：
Hong Zhang;Alexander J. E. Novak;Cooper S. Jamieson;Xiao-song Xue;Shuming Chen;D. Trauner;K. Houk

Natural product anticipation through synthesis.

通过合成的天然产品预期。

DOI：
10.1038/s41570-021-00345-7
发表时间：
2022-03
期刊：
NATURE REVIEWS CHEMISTRY
影响因子：
36.3
作者：
Hetzler, Belinda E.;Trauner, Dirk;Lawrence, Andrew L.
通讯作者：
Lawrence, Andrew L.

Biomimetic Synthesis of (+)-Aspergillin PZ.

DOI：
10.1002/anie.201809703
发表时间：
2018-11-19
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
0
作者：
Reyes JR;Winter N;Spessert L;Trauner D
通讯作者：
Trauner D

Optical Manipulation of F-Actin with Photoswitchable Small Molecules.

DOI：
10.1021/jacs.9b12898
发表时间：
2020-05-20
期刊：
Journal of the American Chemical Society
影响因子：
15
作者：
Borowiak M;Küllmer F;Gegenfurtner F;Peil S;Nasufovic V;Zahler S;Thorn-Seshold O;Trauner D;Arndt HD
通讯作者：
Arndt HD

Complex Natural Products Derived from Pyrogallols.

源自连苯三酚的复杂天然产品。