Photopharmacological Manipulation of Mammalian CRY1 for Regulation of the Circadian Clock.

ABSTRACT: CRY1 and CRY2 proteins are highly conserved components of the circadian clock that controls daily physiological rhythms. Disruption of CRY functions are related to many diseases, including circadian sleep phase disorder. Development of isoform-selective and spatiotemporally controllable tools will facilitate the understanding of shared and distinct functions of CRY1 and CRY2. Here, we developed CRY1-selective compounds that enable light-dependent manipulation of the circadian clock. From phenotypic chemical screening in human cells, we identified benzophenone derivatives that lengthened the circadian period. These compounds selectively interacted with the CRY1 photolyase homology region, resulting in activation of CRY1 but not CRY2. The benzophenone moiety rearranged a CRY1 region called t

SUBMITTER: Kolarski D 

PROVIDER: S-EPMC7863067 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature