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

preprint
submitted on 27.02.2021, 13:18 and posted on 01.03.2021, 12:54 by Alexander Sailer, Joyce Meiring, Constanze Heise, Linda Pettersson, Anna Akhmanova, Julia Thorn-Seshold, Oliver Thorn-Seshold

Photoswitchably bioactive reagents, known as “photopharmaceuticals”, promise powerful applications in high-precision biological research. Yet most photoswitch scaffolds cannot be quantitatively bidirectionally photoisomerised, so they suffer from residual background activity that can confound experiments. We rationally designed photopharmaceuticals using the emerging near-quantitative photoswitch pyrrole hemithioindigo (PHTubs), to isomer-specifically inhibit the cytoskeletal protein tubulin. These PHTub reagents allow simultaneous visible-light imaging and photoswitching in live cells, where they could be used for cell-precise photomodulation of microtubule dynamics, and photocontrol over cell cycle progression and cell death. This is, as far as we know, the first use of a hemithioindigo photopharmaceutical for high-spatiotemporal-resolution biological control in live cells. This work opens up new horizons for high-precision microtubule research using PHTubs; and shows the cellular applicability of the near-quantitative photoswitch pyrrole hemithioindigo as a valuable scaffold for photocontrol of a range of other biological targets.

Funding

Emmy Noether grant number 400324123

SFB 1032 project B09 number 201269156

SFB TRR 152 project P24 number 239283807

SPP 1926 project XVIII number 426018126

History

Email Address of Submitting Author

oliver.thorn-seshold@cup.lmu.de

Institution

LMU Munich

Country

Germany

ORCID For Submitting Author

0000-0003-3981-651X

Declaration of Conflict of Interest

no conflict of interest

Version Notes

v2.2 20210227 auth

Exports