(S,R,S)-AHPC-PEG3-NH2 hydrochloride

Background Introduction

(S,R,S)-AHPC-PEG3-NH2 hydrochloride is a synthetic E3 ligase ligand-linker conjugate commonly utilized in the development of PROTACs (Proteolysis Targeting Chimeras). It features the well-characterized VHL ligand (AHPC) connected via a triethylene glycol (PEG3) linker, terminating in an amine group ideal for bioconjugation. This modular compound is instrumental for researchers designing highly specific molecular tools to induce targeted protein degradation, a fast-growing area in chemical biology and drug discovery.

Mechanism

The mechanism of (S,R,S)-AHPC-PEG3-NH2 hydrochloride centers on its function as a building block in PROTAC technology. The AHPC moiety selectively binds to the VHL (von Hippel-Lindau) E3 ligase. The PEG3 linker provides optimal flexibility and solubility, while the terminal amine (NH2) allows for easy conjugation to other ligands or small molecules that target the protein of interest. When incorporated into a PROTAC, this conjugate brings the E3 ligase into proximity with the target protein, facilitating its ubiquitination and subsequent degradation via the proteasome pathway.

Applications

(S,R,S)-AHPC-PEG3-NH2 hydrochloride is widely used in the synthesis of custom PROTAC molecules for both in vitro and in vivo studies. Its primary applications include drug discovery screening, target validation, and mechanistic studies of protein homeostasis. Researchers utilize this ligand-linker conjugate to generate bifunctional molecules capable of selective degradation of disease-relevant proteins, thus advancing the development of next-generation therapeutics, particularly in oncology, neurodegenerative disorders, and immunology.

• PEG3 linker provides enhanced water solubility and optimal spatial flexibility for efficient PROTAC design.
• Amine termination enables versatile conjugation for rapid synthesis of VHL-based PROTAC molecules.