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Photopharmacological modulation of native CRAC channels using azoboronate photoswitches.

ABSTRACT: SignificanceCalcium release-activated calcium (CRAC) channels play key roles in the regulation of cellular signaling, transcription, and migration. Here, we describe the design, chemical synthesis, and characterization of photoswitchable channel inhibitors that can be switched on and off depending on the wavelength of light used. We use the compounds to induce light-dependent modulation of channel activity and downstream gene expression in human immune cells. We further expand the usage of the compounds to control seeding of cancer cells in target tissue and regulation of response to noxious stimuli in vivo in mice.

SUBMITTER: Udasin R

PROVIDER: S-EPMC9060504 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Photopharmacological modulation of native CRAC channels using azoboronate photoswitches.

Udasin Ronald R Sil Anwesha A Zomot Elia E Achildiev Cohen Hadas H Haj Jozafina J Engelmayer Nurit N Lev Shaya S Binshtok Alexander M AM Shaked Yuval Y Kienzler Michael A MA Palty Raz R

Proceedings of the National Academy of Sciences of the United States of America 20220321 13

SignificanceCalcium release-activated calcium (CRAC) channels play key roles in the regulation of cellular signaling, transcription, and migration. Here, we describe the design, chemical synthesis, and characterization of photoswitchable channel inhibitors that can be switched on and off depending on the wavelength of light used. We use the compounds to induce light-dependent modulation of channel activity and downstream gene expression in human immune cells. We further expand the usage of the c ...[more]

PMID: 35312368

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