Quantitative control of subcellular protein localization with a photochromic dimerizer.

Artificial control of intracellular protein dynamics with high precision provides deep insight into complicated biomolecular networks. Optogenetics and caged compound-based chemically induced dimerization (CID) systems are emerging as tools for spatiotemporally regulating intracellular protein dynamics. However, both technologies face several challenges for accurate control such as the duration of activation, deactivation rate and repetition cycles.

Arylazopyrazole-Based Photoswitchable Inhibitors Selective for Dihydrofolate Reductase.

Selective inhibitors of dihydrofolate reductase (eDHFR) are crucial chemical biology tools that have widespread clinical applications. We developed a set of eDHFR-selective photoswitchable inhibitors by derivatizing the structure of our previously reported methotrexate (MTX) azolog, . Substitution of the skeletal -phenylene group of azoMTX with bulky bis-alkylated arylazopyrazole moieties significantly increased its selectivity toward eDHFR over human DHFR.