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

Background Introduction

(S,R,S)-AHPC-PEG5-NH2 is a highly versatile E3 ligase ligand-linker conjugate designed for use in targeted protein degradation technologies, particularly PROTAC (Proteolysis Targeting Chimera) synthesis. It combines a high-affinity VHL (von Hippel-Lindau) ligand (AHPC) with a PEG5 (polyethylene glycol 5) linker terminated by a reactive amine (NH2) group, enabling seamless attachment to diverse warheads or targeting ligands.

Mechanism

(S,R,S)-AHPC-PEG5-NH2 operates by harnessing the PROTAC strategy, in which this bifunctional molecule serves as the E3 ubiquitin ligase recruiting module. The AHPC moiety specifically binds to the VHL E3 ligase, while the PEG5 linker provides an optimal distance and flexibility to connect with a target protein ligand (via the terminal amine group). Upon development into a PROTAC, the molecule induces the proximity-driven ubiquitination and subsequent proteasomal degradation of the target protein, effectively reducing its cellular levels.

Applications

(S,R,S)-AHPC-PEG5-NH2 is indispensable in the rational design and synthesis of PROTACs for research and drug discovery. Its long, flexible PEG5 linker enhances cell permeability and pharmacokinetic properties, making it suitable for developing next-generation degraders against disease-relevant proteins. Researchers use this reagent to create novel therapeutics for oncology, neurodegenerative disorders, and other conditions linked to aberrant protein expression. Additionally, its amine terminus facilitates straightforward conjugation with a variety of targeting ligands via amide coupling chemistry.

• Long PEG5 linker provides optimal spatial distance for effective PROTAC design, improving target protein degradation efficiency.
• Terminal amine group enables versatile and efficient attachment to target protein ligands, facilitating streamlined PROTAC synthesis workflows.