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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 18, 2020
- Source ID
- 10.1038/s41467-020-18377-w
Entities
People
- Alan L. Leggett
- Amanda Robichaud
- Amy S. Conway
- Behnam Nabet
- Bo Kyung A. Seong
- Dennis L. Buckley
- Fleur M Ferguson
- James E. Bradner
- Joseph D Mancias
- Kimberly Stegmaier
- Mikaela L. Mohardt
- Miljan Kuljanin
- Nathanael Gray
Organizations
- American Cancer Society
- Burroughs Wellcome Fund
- Damon Runyon Cancer Research Foundation
- National Cancer Institute
- United States Department of Defense
- United States Department of Health and Human Services