(S,R,S)-AHPC-Boc

Background Introduction

(S,R,S)-AHPC-Boc is a derivative of the von Hippel-Lindau (VHL) E3 ligase ligand, widely utilized in targeted protein degradation technologies such as PROTACs (Proteolysis Targeting Chimeras). AHPC (hydroxyproline-based VHL ligand) features a specific stereochemistry crucial for selective binding to the VHL E3 ligase complex. The Boc (tert-butyloxycarbonyl) protection on the amine group further enhances its chemical stability and provides a convenient synthetic handle for downstream conjugation steps in PROTAC design. This high-purity intermediate is a key starting material for building next-generation VHL-recruiting degraders.

Mechanism

(S,R,S)-AHPC-Boc targets the VHL E3 ubiquitin ligase by mimicking the essential hydroxyproline motif recognized by the VHL protein. Upon incorporation into a bifunctional PROTAC molecule, it recruits the VHL complex to proximity with the target protein ligand. This spatial arrangement leads to ubiquitination of the target protein, facilitating its recognition and degradation by the ubiquitin-proteasome system. The Boc group temporarily protects the amine moiety during synthesis and can be readily removed for further functionalization, supporting versatile linker and ligand attachment strategies.

Applications

(S,R,S)-AHPC-Boc serves as a highly efficient reagent for constructing VHL-based PROTACs and other protein degraders. Its primary use is in medicinal chemistry and chemical biology research focused on targeted protein degradation. Typical applications include:

• Synthesis of VHL E3 ligase ligands incorporated into PROTACs
• Drug discovery projects exploring novel therapeutics for undruggable targets
• SAR and medicinal chemistry studies to optimize degrader potency and selectivity
• Generation of custom protein degraders for target validation and mechanism-of-action studies
• Outsourced CRO synthesis and academic research projects developing next-generation TPD molecules

• High-purity compound verified by HPLC, NMR, and LC-MS
• Consistent batch-to-batch reproducibility with complete QC documentation
• Supplied with COA, MSDS, and analytical data for traceability
• Reliable global shipping with stability-guaranteed packaging
• Dedicated technical support and optional custom synthesis service
• Demonstrates strong binding affinity to CRBN, VHL, or other E3 ligases
• Enables stable E3 ligase recruitment for targeted protein degradation
• Boc-protected linker enhances synthetic flexibility and preserves AHPC integrity during PROTAC assembly.
• Optimized for VHL E3 ligase recruitment, facilitating efficient and selective protein degradation in targeted therapies.