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Targeted protein oxidation using a chromophore-modified rapamycin analog† † Electronic supplementary information (ESI) available. See DOI: 10.1039/d1sc04464h

ABSTRACT: Chemically induced dimerization of FKBP and FRB using rapamycin and rapamycin analogs has been utilized in a variety of biological applications. Formation of the FKBP-rapamycin-FRB ternary complex is typically used to activate a biological process and this interaction has proven to be essentially irreversible. In many cases, it would be beneficial to also have temporal control over deactivating a biological process once it has been initiated. Thus, we developed the first reactive oxygen species-generating rapamycin analog toward this goal. The BODIPY-rapamycin analog BORap is capable of dimerizing FKBP and FRB to form a ternary complex, and upon irradiation with 530 nm light, generates singlet oxygen to oxidize and inactivate proteins of interest fused to FKBP/FRB. Utilization of a ROS-generating chromophore for the development of reversible control of rapamycin-induced protein dimerization via targeted oxidation.

SUBMITTER: Courtney T

PROVIDER: S-EPMC8528027 | biostudies-literature |

REPOSITORIES: biostudies-literature

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