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Angew Chem Int Ed Engl ; 60(44): 23695-23704, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34460143

RESUMO

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.


Assuntos
Antimitóticos/metabolismo , Índigo Carmim/análogos & derivados , Microtúbulos/metabolismo , Pirróis/metabolismo , Análise de Célula Única , Antimitóticos/química , Ciclo Celular , Morte Celular , Linhagem Celular Tumoral , Células HeLa , Humanos , Índigo Carmim/química , Índigo Carmim/metabolismo , Microtúbulos/química , Estrutura Molecular , Processos Fotoquímicos , Pirróis/química
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