Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules.

ABSTRACT: Chemical biology strategies for directly perturbing protein homeostasis including the degradation tag (dTAG) system provide temporal advantages over genetic approaches and improved selectivity over small molecule inhibitors. We describe dTAG^V-1, an exclusively selective VHL-recruiting dTAG molecule, to rapidly degrade FKBP12^F36V-tagged proteins. dTAG^V-1 overcomes a limitation of previously reported CRBN-recruiting dTAG molecules to degrade recalcitrant oncogenes, supports combination degrader studies and facilitates investigations of protein function in cells and mice.

SUBMITTER: Nabet B 

PROVIDER: S-EPMC7501296 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature