Gene

Function (biology)

Cell biology

Target protein

Biology

Small molecule

Biochemistry

Molecule

Computational biology

Organic chemistry

Protein function

Chemistry

Chemical biology

Protein degradation

Nature Communications

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.

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