(S,R,S)-AHPC-C6-NH2 dihydrochloride

Background Introduction

(S,R,S)-AHPC-C6-NH2 dihydrochloride is a specialized E3 ligase ligand-linker conjugate widely utilized in the development of PROTACs (Proteolysis Targeting Chimeras). As a derivative of the well-characterized AHPC (aryl hydroxyproline carboxamide), it is engineered to recruit the von Hippel-Lindau (VHL) E3 ligase, a key player in ubiquitin-mediated protein degradation. The compound features a flexible hexyl (C6) linker terminated with an amino (NH2) group, optimized for efficient conjugation to target-binding ligands.

Mechanism

(S,R,S)-AHPC-C6-NH2 dihydrochloride functions as a bifunctional building block in PROTAC design. The AHPC moiety selectively binds to the VHL E3 ubiquitin ligase complex, while the C6-NH2 linker enables straightforward attachment to small molecule ligands or peptides specific for the protein of interest. Upon cellular delivery, PROTAC molecules incorporating this conjugate simultaneously engage the target protein and VHL ligase, facilitating the formation of a ternary complex. This proximity triggers ubiquitination and subsequent proteasomal degradation of the target protein, allowing for precise and catalytic removal of disease-associated proteins.

Applications

This VHL ligand-linker conjugate is essential for researchers in drug discovery and chemical biology aiming to create novel PROTACs. Its primary applications include the synthesis of customized PROTAC molecules targeting various disease-associated proteins, especially oncogenic and pathogenic proteins resistant to traditional small molecule inhibitors. (S,R,S)-AHPC-C6-NH2 dihydrochloride is widely used for target validation studies, mechanistic research in targeted protein degradation, and development of next-generation therapeutics in oncology, neurodegeneration, and immunology, offering powerful tools for modulating previously undruggable proteins.

• Amine-terminated C6 linker ensures versatile and stable conjugation with target ligands, optimizing the assembly of potent PROTAC molecules.
• Highly selective VHL E3 ligase recruiter, facilitating efficient ubiquitination and targeted protein degradation applications.