(S,R,S)-AHPC-C8-NH2 dihydrochloride

Background Introduction

(S,R,S)-AHPC-C8-NH2 dihydrochloride is a specialized E3 ligase ligand-linker conjugate designed for use in the development of proteolysis targeting chimeras (PROTACs). PROTAC technology leverages the ubiquitin-proteasome system for targeted protein degradation, and the choice of an effective E3 ligase ligand is essential for the creation of potent and selective PROTAC molecules.

Mechanism

(S,R,S)-AHPC-C8-NH2 dihydrochloride functions as a selective ligand for the von Hippel-Lindau (VHL) E3 ubiquitin ligase. This compound features an (S,R,S)-configured AHPC (hydroxyproline-based) core tethered to an 8-carbon alkyl linker terminated with a primary amine, allowing for conjugation to target protein ligands. When incorporated into a PROTAC, the E3 ligase ligand-linker conjugate bridges the E3 ligase and the protein of interest, inducing proximity that facilitates ubiquitination and subsequent proteasomal degradation of the target protein.

Applications

(S,R,S)-AHPC-C8-NH2 dihydrochloride is widely used in the design and synthesis of VHL-based PROTACs for targeted protein degradation studies. This molecule enables researchers to develop custom PROTACs for the selective elimination of disease-related proteins, supporting investigation of protein function, validation of therapeutic targets, and preclinical drug discovery. Additionally, it serves as a valuable tool for optimizing linker length, facilitating structure-activity relationship studies, and expanding the repertoire of degraders for challenging drug targets in oncology, neurodegeneration, and immunology research.

• Extended C8 linker provides optimal spatial flexibility for VHL-based PROTAC design, facilitating efficient target protein degradation.
• Amine functional group ensures convenient conjugation with diverse ligands, streamlining the synthesis of custom PROTAC molecules.