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Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications.

ACS Chem. Biol.. 2019; 
WardCarl C,KleinmanJordan I,BrittainScott M,LeePatrick S,ChungClive Yik Sham,KimKenneth,PetriYana,ThomasJason R,TallaricoJohn A,McKennaJeffrey M,SchirleMarkus,NomuraDani
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Catalog Antibody Lysates were cleared by centrifugation at 21 000g for 20 min, and resulting supernatant was mixed with 30 μL of anti-FLAG resin (Genscript, L00432) and rotated at 4 °C for 1 h. Get A Quote

摘要

Targeted protein degradation has arisen as a powerful strategy for drug discovery allowing the targeting of undruggable proteins for proteasomal degradation. This approach most often employs heterobifunctional degraders consisting of a protein-targeting ligand linked to an E3 ligase recruiter to ubiquitinate and mark proteins of interest for proteasomal degradation. One challenge with this approach, however, is that only a few E3 ligase recruiters currently exist for targeted protein degradation applications, despite the hundreds of known E3 ligases in the human genome. Here, we utilized activity-based protein profiling (ABPP)-based covalent ligand screening approaches to identify cysteine-reactive smal... More

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