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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 dTAGV-1, an exclusively selective VHL-recruiting dTAG molecule, to rapidly degrade FKBP12F36V-tagged proteins. dTAGV-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

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

DISEASE(S): Disease Free

SUBMITTER: Behnam Nabet

LAB HEAD: Nathanael Gray

PROVIDER: PXD018937 | Pride | 2020-09-21

REPOSITORIES: Pride

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

Nabet Behnam B Ferguson Fleur M FM Seong Bo Kyung A BKA Kuljanin Miljan M Leggett Alan L AL Mohardt Mikaela L ML Robichaud Amanda A Conway Amy S AS Buckley Dennis L DL Mancias Joseph D JD Bradner James E JE Stegmaier Kimberly K Gray Nathanael S NS

Nature communications 20200918 1

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 dTAGV-1, an exclusively selective VHL-recruiting dTAG molecule, to rapidly degrade FKBP12F36V-tagged proteins. dTAGV-1 overcomes a limitation of previously reported CRBN-recruiting dTAG molecules to degrade recalcitrant oncogenes, ...[more]

PMID: 32948771

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