(S,R,S)-AHPC-CO-C6-COOH

Background Introduction

(S,R,S)-AHPC-CO-C6-COOH is a specialized E3 ligase ligand-linker conjugate developed for advancing the design and synthesis of PROTACs (Proteolysis Targeting Chimeras). This molecule features the (S,R,S)-AHPC ligand, which specifically recruits the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex, attached via a flexible hexyl (C6) linker terminated with a carboxylic acid group for modular conjugation. Its design enables researchers to create highly selective protein degraders for targeted protein knockdown applications.

Mechanism

The mechanism of (S,R,S)-AHPC-CO-C6-COOH centers on its use as an E3 ligase recruiting component in PROTAC construction. The (S,R,S)-AHPC moiety binds selectively to the VHL E3 ligase, while the C6 aliphatic linker provides spatial flexibility and the terminal carboxylic acid allows for further chemical coupling. When incorporated into a PROTAC molecule, it facilitates the recruitment of VHL ligase to a target protein, enabling ubiquitination and subsequent proteasomal degradation of the target, thereby reducing its cellular levels with high specificity.

Applications

(S,R,S)-AHPC-CO-C6-COOH finds broad application in academic and pharmaceutical research focused on targeted protein degradation. It serves as a modular building block for synthesizing VHL-based PROTACs, allowing the exploration of various disease-relevant targets, including oncogenic proteins and epigenetic regulators. Its optimized structure supports the development of next-generation therapeutics and chemical biology tools for validated target identification, mechanism-of-action studies, and drug discovery pipelines aimed at undruggable proteins.

• Tailored for VHL-based PROTAC design, ensuring selective and potent protein degradation.
• C6 aliphatic linker provides optimal spatial flexibility for efficient target protein engagement and ligand conjugation.