Application

Protein degrader builiding block (S,R,S)-AHPC-C₆-PEG₃-butyl Chloride enables the synthesis of molecules for targeted protein degradation and PROTAC (proteolysis-targeting chimeras) technology. This conjugate contains a von Hippel–Lindau (VHL)-recruiting ligand, a linker with both hydrophobic and hydrophilic moieties, and a pendant chloroalkane for reactivity with a nucleophilic group on a 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 pendant chloro group, 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 DegradationModular PROTAC Design for the Degradation of Oncogenic BCR-ABLTargeted Protein Degradation by Small MoleculesSmall-Molecule PROTACS: New Approaches to Protein DegradationTargeted Protein Degradation: from Chemical Biology to Drug DiscoveryImpact of linker length on the activity of PROTACs