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MilliporeSigma Sigma Organics products encompass a wide range of quality reagents, solvents, catalysts, and building blocks for organic synthesis. From benchtop discovery to process development and scale-up, Sigma Organics solutions are built to meet the needs of synthetic chemists.
Protein degrader building block(S,R,S)-VL285 Phenol-methylamino-PEG1-NH2 hydrochloride 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 with alternative exit vector from the widely used VH032 ((901490), a linker, 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.Technology Spotlight: Degrader Building Blocks for Targeted Protein DegradationPortal: Building PROTAC™ Degraders for Targeted Protein DegradationTargeted Protein Degradation by Small MoleculesTargeted Protein Degradation: from Chemical Biology to Drug DiscoveryHaloPROTACS: Use of Small Molecule PROTACs to Induce Degradation of HaloTag Fusion ProteinsDifferential PROTAC substrate specificity dictated by orientation of recruited E3 ligasePROTAC is a registered trademark of Arvinas Operations, Inc., and is used under license
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