(S,R,S)-AHPC-PEG5-NH2 hydrochloride

Background Introduction

(S,R,S)-AHPC-PEG5-NH2 hydrochloride is a high-purity E3 ligase ligand-linker conjugate designed specifically for targeted protein degradation research. This versatile building block is a derivative of (S,R,S)-AHPC (aryl hydrocarbon receptor-interacting protein/hydroxyproline-conjugated), a potent ligand for the von Hippel-Lindau (VHL) E3 ubiquitin ligase, and incorporates a PEG5 (pentaethylene glycol) linker with a terminal amine functional group. The hydrochloride salt form guarantees enhanced solubility and stability, making it an ideal tool for constructing highly efficient PROTAC (Proteolysis Targeting Chimera) molecules.

Mechanism

(S,R,S)-AHPC-PEG5-NH2 hydrochloride functions by bridging a target protein and the cellular ubiquitination machinery via the VHL E3 ligase. The (S,R,S)-AHPC moiety selectively binds to VHL, while the PEG5 linker provides optimal spatial flexibility and improves solubility. The terminal amine enables facile conjugation to various target ligands or pharmacophores. In PROTAC applications, this conjugate is covalently attached to a ligand that recognizes a protein of interest, forming a bifunctional molecule. The resultant PROTAC simultaneously recruits VHL and the target protein into proximity, leading to target ubiquitination and subsequent proteasomal degradation.

Applications

(S,R,S)-AHPC-PEG5-NH2 hydrochloride is widely used in the development and optimization of PROTACs for chemical biology and drug discovery. It enables the rapid assembly of new PROTAC molecules targeting challenging or "undruggable" proteins implicated in cancer, neurodegenerative disorders, and other diseases. Researchers employ this reagent for early-stage screening, structure-activity relationship (SAR) studies, and proof-of-concept degradation experiments. Additionally, its PEG5 linker enhances pharmacokinetics and cellular permeability of final PROTAC molecules, making it a valuable asset in preclinical therapeutic development and mechanistic studies of targeted protein degradation.

• High-affinity VHL ligand ensures effective recruitment of E3 ubiquitin ligase for targeted protein degradation.
• PEG5 linker enhances aqueous solubility and improves pharmacokinetic properties for advanced PROTAC development.