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Sailer, Alexander; Meiring, Joyce C. M.; Heise, Constanze; Pettersson, Linda N.; Akhmanova, Anna; Thorn‐Seshold, Julia; Thorn‐Seshold, Oliver
Angewandte Chemie, October 25, 2021, Letnik: 133, Številka: 44Journal Article
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. Pyrrole hemithioindigos can be near‐quantitatively photoisomerised by the laser wavelengths available on confocal microscopes. The first pyrrole hemithioindigo‐based photopharmaceuticals, PHTubs, which are photoswitchable tubulin inhibitors, have been developed. PHTubs optically inhibit microtubule dynamics in live cells with single‐cell, second‐scale spatiotemporal precision, with both lit‐active and dark‐active compounds demonstrated in action.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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