Application

Protein degrader building block CCW16-PEG₂-butyl-BocNH enables the synthesis of molecules for targeted protein degradation and PROTAC (proteolysis-targeting chimeras) technology. This conjugate contains a RING finger protein 4 (RNF4)-recruiting ligand, a linker with both hydrophobic and hydrophilic moieties, and a pendant amine for reactivity with a carboxylic acid on the target ligand. Because even slight alterations in ligands and crosslinkers can affect ternary complex formation between the target, E3 ligase, and PROTAC, many analogs are prepared to screen for optimal target degradation. When used with other protein degrader building blocks with a terminal amine, parallel synthesis can be used to more quickly generate PROTAC libraries that feature variation in crosslinker length, composition, and E3 ligase ligand.

Legal Information

PROTAC is a registered trademark of Arvinas Operations, Inc., and is used under license

Other Notes

Technology Spotlight: Degrader Building Blocks for Targeted Protein DegradationPortal: Building PROTAC^® Degraders for Targeted Protein DegradationCovalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applicationstargeted protein degradationTargeted Protein Degradation by Small Molecules Small-Molecule PROTACS: New Approaches to Protein DegradationTargeted Protein Degradation: from Chemical Biology to Drug Discovery