Photoswitchable Epothilone-Based Microtubule Stabilisers Allow GFP-Imaging-Compatible, Optical Control over the Microtubule Cytoskeleton.
Photoswitchable Epothilone-Based Microtubule Stabilisers Allow GFP-Imaging-Compatible, Optical Control over the Microtubule Cytoskeleton.
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DOI：
10.1002/anie.202114614
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发表时间：
2022-03-01
影响因子：
16.6
通讯作者：
Thorn-Seshold, Oliver
中科院分区：
文献类型：
--
作者：
Gao, Li;Meiring, Joyce C. M.;Heise, Constanze;Rai, Ankit;Mueller-Deku, Adrian;Akhmanova, Anna;Thorn-Seshold, Julia;Thorn-Seshold, Oliver
调节微管动力学的光学方法有望达到解密细胞骨架在生物学中的作用所需的微米和毫秒级分辨率。然而，光学微管稳定剂的开发不足。我们引入“STEpos”作为GFP正交的、基于埃坡霉素的光响应微管稳定剂。他们在设计中使用了一种新型的苯乙烯基噻唑光开关来调节控制埃博霉素效力的氢键和空间效应。STEpos以微米和秒级时空精度控制微管动力学和细胞分裂。与以前的光学微管稳定剂相比，它们大大提高了效力，溶解度和易用性，这项工作中的结构-光开关-活性关系见解将指导未来的优化。STEpo试剂可为细胞骨架生物物理学、货物运输、细胞运动、细胞分裂、发育和神经科学的高精度研究做出巨大贡献。介绍了一种基于光开关埃坡霉素的微管稳定剂STEpo，用于活细胞中的高精度细胞骨架光控制。STEpo的特点是一种新型的苯乙烯基噻唑光开关，对偶氮苯是等排的，但与GFP成像兼容，并且可以光调制氢键和空间。STEpo以微米和秒级分辨率光控制微管动力学和细胞分裂，并具有中纳摩尔效力。
Optical methods to modulate microtubule dynamics show promise for reaching the micron‐ and millisecond‐scale resolution needed to decrypt the roles of the cytoskeleton in biology. However, optical microtubule stabilisers are under‐developed. We introduce “STEpos” as GFP‐orthogonal, light‐responsive epothilone‐based microtubule stabilisers. They use a novel styrylthiazole photoswitch in a design to modulate hydrogen‐bonding and steric effects that control epothilone potency. STEpos photocontrol microtubule dynamics and cell division with micron‐ and second‐scale spatiotemporal precision. They substantially improve potency, solubility, and ease‐of‐use compared to previous optical microtubule stabilisers, and the structure‐photoswitching‐activity relationship insights in this work will guide future optimisations. The STEpo reagents can contribute greatly to high‐precision research in cytoskeleton biophysics, cargo transport, cell motility, cell division, development, and neuroscience. A photoswitchable epothilone‐based microtubule stabiliser, STEpo, is introduced for high‐precision cytoskeleton photocontrol in live cells. STEpo features a novel styrylthiazole photoswitch that is isosteric to azobenzene, but is compatible with GFP imaging, and can photomodulate hydrogen‐bonding as well as sterics. STEpo photocontrols microtubule dynamics and cell division with micron‐ and second‐scale resolution, and has mid‐nanomolar potency.
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影响因子：
4.5
作者：
An, Yang;Chen, Chao;Wang, Zheng
通讯作者：
Wang, Zheng
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
影响因子：
8.6
作者：
Gao, Li;Meiring, Joyce C. M.;Thorn-Seshold, Oliver
通讯作者：
Thorn-Seshold, Oliver
影响因子：
2.7
作者：
Gavin, Jason;Ruiz, Juan F. Marquez;Gilmer, John F.
通讯作者：
Gilmer, John F.
影响因子：
8.6
作者：
Leinders-Zufall, Trese;Storch, Ursula;Zufall, Frank
通讯作者：
Zufall, Frank