Biological and Medicinal Chemistry

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

Abstract

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.

Version notes

v2.2 20210227 auth

Content

Thumbnail image of Thorn-Seshold (Sailer) 2021 PHTub Main v2.2.pdf

Supplementary material

Thumbnail image of Thorn-Seshold (Sailer) 2021 PHTub Supp v5.5 nmr.pdf
Thorn-Seshold (Sailer) 2021 PHTub Supp v5.5 nmr
Thumbnail image of Thorn-Seshold (Sailer) 2021 PHTub Supp Movies.zip
Thorn-Seshold (Sailer) 2021 PHTub Supp Movies