Pyrrole Hemithioindigo Antimitotics with Near-Quantitative Bidirectional Photoswitching that Photocontrol Cellular Microtubule Dynamics with Single-Cell Precision**

Sailer, Alexander; Meiring, Joyce C. M.; Heise, Constanze; Pettersson, Linda N.; Akhmanova, Anna; Thorn-Seshold, Julia und Thorn-Seshold, Oliver (2021): Pyrrole Hemithioindigo Antimitotics with Near-Quantitative Bidirectional Photoswitching that Photocontrol Cellular Microtubule Dynamics with Single-Cell Precision**. In: Angewandte Chemie-International Edition, Vol. 60, No. 44: pp. 23695-23704

Abstract

We report the first cellular application of the emerging near-quantitative photoswitch pyrrole hemithioindigo, by rationally designing photopharmaceutical PHTub inhibitors of the cytoskeletal protein tubulin. PHTubs allow simultaneous visible-light imaging and photoswitching in live cells, delivering cell-precise photomodulation of microtubule dynamics, and photocontrol over cell cycle progression and cell death. This is the first acute use of a hemithioindigo photopharmaceutical for high-spatiotemporal-resolution biological control in live cells. It additionally demonstrates the utility of near-quantitative photoswitches, by enabling a dark-active design to overcome residual background activity during cellular photopatterning. This work opens up new horizons for high-precision microtubule research using PHTubs and shows the cellular applicability of pyrrole hemithioindigo as a valuable scaffold for photocontrol of a range of other biological targets.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy > Department of Pharmacy
• Subjects: 500 Science > 540 Chemistry
• ISSN: 1433-7851
• Language: English