(S,R,S)-AHPC-CO-PEG1-COOH

Background Introduction

(S,R,S)-AHPC-CO-PEG1-COOH is a specialized E3 ligase ligand-linker conjugate primarily employed in the design and synthesis of Proteolysis Targeting Chimeras (PROTACs). As part of the ever-evolving targeted protein degradation field, this compound is engineered for optimal engagement with the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex, facilitating the rapid and selective removal of disease-relevant proteins within cells.

Mechanism

The mechanism of (S,R,S)-AHPC-CO-PEG1-COOH centers on its bifunctional characteristics. One end of the molecule contains the (S,R,S)-AHPC moiety, which acts as a highly specific ligand for the VHL E3 ligase. The other end of the molecule features a carboxylic acid group, connected via a short PEG1 linker, which can be chemically conjugated to a ligand for a protein of interest. When assembled into a PROTAC molecule, (S,R,S)-AHPC-CO-PEG1-COOH brings the target protein and the VHL E3 ligase into close spatial proximity, enabling the transfer of ubiquitin molecules to the target. This ubiquitination signals the target protein for subsequent degradation by the proteasome.

Applications

(S,R,S)-AHPC-CO-PEG1-COOH is a powerful tool in drug discovery and chemical biology research. It serves as a modular linker-ligand scaffold for constructing novel PROTAC molecules aimed at degrading various disease-associated proteins. Researchers use it to study protein function, validate drug targets, and develop potential therapeutics for cancer, neurodegenerative disorders, and other conditions where selective protein degradation offers a therapeutic advantage. Its PEG1-linker provides suitable solubility and flexibility, supporting the design of PROTACs with favorable pharmacokinetic profiles.

• PEGylated linker improves aqueous solubility and bioavailability for efficient PROTAC development.
• Optimized VHL E3 ligase ligand ensures high selectivity and potency in targeted protein degradation applications.