(S,R,S)-AHPC-PEG1-Alkyne

Background Introduction

(S,R,S)-AHPC-PEG1-Alkyne is a specialized E3 ligase ligand-linker conjugate designed for use in targeted protein degradation. This molecule combines the high-affinity von Hippel-Lindau (VHL) E3 ligase ligand (AHPC), a short PEG1 linker, and an alkyne functional group for bioorthogonal conjugation, making it highly valuable for assembling proteolysis targeting chimeras (PROTACs). By facilitating the development of customizable PROTAC molecules, (S,R,S)-AHPC-PEG1-Alkyne offers a powerful tool for selective and efficient protein degradation in drug discovery and biological research.

Mechanism

(S,R,S)-AHPC-PEG1-Alkyne acts as an E3 ligase recruiting module in PROTAC technology. The AHPC moiety specifically binds to the VHL E3 ligase, enabling recruitment of the cellular ubiquitination machinery. The PEG1 linker provides spatial flexibility, while the terminal alkyne group allows for efficient coupling with a ligand for a protein of interest, often via click chemistry. Once conjugated, the resulting PROTAC molecule brings the target protein into close proximity with the VHL E3 ligase, leading to ubiquitination and subsequent proteasomal degradation of the target protein within the cell.

Applications

(S,R,S)-AHPC-PEG1-Alkyne is widely employed in the synthesis of customized PROTACs for targeted protein degradation studies. Its alkyne group enables modular assembly with a broad range of ligands via click chemistry, supporting high-throughput library generation. Researchers use (S,R,S)-AHPC-PEG1-Alkyne in cancer research, neuroscience, and drug discovery to explore the function of disease-relevant proteins and identify potent therapeutic strategies. Its versatility and compatibility with VHL-based target degradation pathways make it an indispensable tool in modern chemical biology and medicinal chemistry applications.

• Alkyne-functionalized PEG1 linker enables efficient and versatile conjugation via click chemistry for streamlined PROTAC assembly.
• Designed for VHL E3 ligase recruitment, facilitating targeted protein degradation in cutting-edge PROTAC research and drug discovery.