Partial PROTAC (S,R,S)-AHPC-C6-CO2H 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 and an alkyl-chain crosslinker with pendant carboxylic acid for reactivity with an amine 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 Partial PROTACs with a pendant carboxyl group, parallel synthesis can be used to more quickly generate PROTAC libraries that feature variation in crosslinker length, composition, and E3 ligase ligand.

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