Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules
Behnam Nabet(Harvard University), Fleur M. Ferguson(Harvard University), Bo Kyung A. Seong(Broad Institute), Miljan Kuljanin(Dana-Farber Cancer Institute), Alan L. Leggett(Dana-Farber Cancer Institute), Mikaela L. Mohardt(Dana-Farber Cancer Institute), Amanda L. Robichaud(Dana-Farber Cancer Institute), Amy Saur Conway(Dana-Farber Cancer Institute), Dennis L. Buckley(Dana-Farber Cancer Institute), Joseph D. Mancias(Dana-Farber Cancer Institute), James E. Bradner(Harvard University), Kimberly Stegmaier(Broad Institute), Nathanael S. Gray(Harvard University)
Cited by 310Open Access
Abstract
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.
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