(S,R,S)-AHPC-PEG2-NH2

Background Introduction

(S,R,S)-AHPC-PEG2-NH2 is a specialized E3 ligase ligand-linker conjugate designed for use in the development of proteolysis targeting chimeras (PROTACs). The molecule features the (S,R,S)-AHPC moiety, a high-affinity VHL E3 ligase ligand, conjugated to a short, hydrophilic PEG2 linker terminated with an amine group for efficient coupling with target protein ligands. This structure enables rapid and reliable assembly of custom PROTAC molecules for both in vitro and in vivo applications.

Mechanism

The mechanism of action for (S,R,S)-AHPC-PEG2-NH2 is rooted in the targeted protein degradation process facilitated by PROTAC technology. The (S,R,S)-AHPC moiety binds selectively to the Von Hippel-Lindau (VHL) E3 ubiquitin ligase, while the PEG2-NH2 linker serves as a flexible spacer for attachment to a ligand that recognizes the desired protein of interest. Once synthesized into a bifunctional PROTAC, the molecule brings the target protein into proximity with the VHL E3 ligase, leading to its ubiquitination and subsequent proteasomal degradation. The PEG2 linker ensures optimal spatial orientation and solubility, improving the PROTAC’s bioactivity and pharmacokinetic properties.

Applications

(S,R,S)-AHPC-PEG2-NH2 is widely employed in the design and synthesis of VHL-recruiting PROTACs for targeted protein degradation research. Its robust performance makes it ideal for projects aiming to elucidate disease-relevant protein functions, validate novel drug targets, and develop next-generation therapeutics in oncology, neurodegeneration, and immunology. This conjugate is also used in high-throughput screening assays, cell-based studies, and preclinical validation of PROTAC efficacy, streamlining the discovery and optimization of new chemical entities for drug development pipelines.