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

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.