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

Background Introduction

(S,R,S)-AHPC-PEG2-Alkyne is a specialized E3 ligase ligand-linker conjugate designed for use in targeted protein degradation research and drug discovery. Based on the small molecule AHPC, a highly selective ligand for the VHL (von Hippel-Lindau) E3 ligase, this tool compound features a PEG2 spacer and an alkyne functional group, making it highly versatile for constructing novel PROTACs (Proteolysis Targeting Chimeras) via click chemistry. Tailored for superior solubility and reactivity, (S,R,S)-AHPC-PEG2-Alkyne is a valuable asset for researchers developing next-generation therapeutics targeting disease-relevant proteins.

Mechanism

(S,R,S)-AHPC-PEG2-Alkyne functions as an E3 ligase recruiting moiety in PROTAC technology. When incorporated into a PROTAC molecule, the AHPC unit binds specifically to the VHL E3 ubiquitin ligase complex. The PEG2 linker adds flexibility and optimal spatial orientation, while the alkyne group enables efficient conjugation to a wide range of target protein ligands using click chemistry. Upon successful recruitment, the resultant PROTAC molecule brings the VHL ligase and the protein of interest into close proximity, facilitating ubiquitination and subsequent degradation of the target protein via the proteasome pathway.

Applications

(S,R,S)-AHPC-PEG2-Alkyne is widely employed in the design and synthesis of custom PROTACs for protein degradation studies. Its alkyne handle allows for modular assembly with different target ligands, accelerating the development of PROTAC libraries for target validation and early-stage drug discovery. Common research applications include the generation of VHL-based PROTACs for oncology, neurodegenerative disease, and immunological disorder research. Its versatility also makes it suitable for live-cell degradation assays, mechanistic studies, and structure-activity relationship (SAR) exploration. By enabling selective degradation of disease-related proteins, (S,R,S)-AHPC-PEG2-Alkyne contributes substantially to advancing targeted protein degradation as a therapeutic strategy.

• Alkyne-modified PEG2 linker enables efficient and versatile click chemistry for rapid PROTAC assembly.
• High affinity for VHL E3 ligase, ensuring potent and selective protein degradation in targeted therapies.