(S,R,S)-AHPC-PEG6-NH2 hydrochloride

Background Introduction

(S,R,S)-AHPC-PEG6-NH2 hydrochloride is a specialized E3 ligase ligand-linker conjugate, designed for use in targeted protein degradation technologies such as PROTACs (Proteolysis Targeting Chimeras). By combining the well-characterized ligand AHPC, which specifically binds to the von Hippel-Lindau (VHL) E3 ubiquitin ligase, with a PEG6 linker and terminal amino functionality, this compound enables efficient coupling and versatile assembly for custom PROTAC development. The increasing demand for flexible, high-purity E3 ligase-linker conjugates in pharmaceutical and chemical biology research underscores the relevance of (S,R,S)-AHPC-PEG6-NH2 hydrochloride.

Mechanism

(S,R,S)-AHPC-PEG6-NH2 hydrochloride operates as a bifunctional component in PROTAC technology. The AHPC moiety binds selectively and tightly to the VHL E3 ubiquitin ligase, recruiting this complex for downstream ubiquitination. The PEG6 linker imparts water solubility and optimal spatial orientation, minimizing steric hindrance between the E3 ligase and the targeted protein of interest. The terminal NH2 group allows straightforward conjugation with various ligands or warheads that recognize disease-related proteins. Upon proper assembly into a PROTAC molecule, the compound facilitates proximity-induced ubiquitination and subsequent proteasomal degradation of the target protein.

Applications

This E3 ligase ligand-linker conjugate is widely used in the rational design and synthesis of PROTACs for targeted protein degradation research. (S,R,S)-AHPC-PEG6-NH2 hydrochloride enables the creation of custom PROTACs against disease-relevant targets in oncology, neurodegeneration, inflammation, and other therapeutic areas. Its application extends to high-throughput screening and validation of degrader molecules in drug discovery programs, supporting chemical biology studies of the ubiquitin-proteasome system, target validation, and mechanism-of-action investigations.