(S,R,S)-AHPC-CO-C8-ACID

Background Introduction

(S,R,S)-AHPC-CO-C8-ACID is an advanced E3 ligase ligand-linker conjugate used widely in the field of targeted protein degradation. As a derivative of AHPC (aryl hydroxyproline carboxylate), this compound is designed to serve as an essential building block for the development of PROTACs (Proteolysis Targeting Chimeras). By integrating a medium-chain alkyl (C8) acid linker, (S,R,S)-AHPC-CO-C8-ACID offers enhanced flexibility and optimal spacing for efficient PROTAC construction, helping researchers drive cutting-edge studies in chemical biology and drug discovery.

Mechanism

The core mechanism of (S,R,S)-AHPC-CO-C8-ACID lies in its ability to recruit the E3 ubiquitin ligase complex, particularly the Von Hippel-Lindau (VHL) ligase, by acting as a high-affinity ligand. The compound’s C8 linker provides versatile conjugation points for attaching target protein ligands or other molecular entities. As part of a bifunctional PROTAC molecule, (S,R,S)-AHPC-CO-C8-ACID brings the target protein into close proximity with the E3 ligase, facilitating ubiquitination of the target protein. This ubiquitinated protein is then recognized and degraded by the proteasome, enabling selective and catalytic protein knockdown within cells.

Applications

(S,R,S)-AHPC-CO-C8-ACID is primarily used in the synthesis of VHL-based PROTACs for targeted protein degradation. Its applications span across oncology, neurodegenerative diseases, and other therapeutic areas where pathological proteins need to be selectively depleted. This E3 ligase ligand-linker conjugate is invaluable for medicinal chemistry research, high-throughput screening, target validation studies, and the development of next-generation therapeutics. Additionally, it supports structure-activity relationship (SAR) exploration by providing a modular linker, enabling researchers to optimize PROTAC efficacy and selectivity.

• Long aliphatic C8 linker optimizes spatial flexibility for efficient VHL E3 ligase recruitment in PROTAC design.
• Carboxylic acid functional group enables versatile conjugation with diverse warheads, facilitating custom PROTAC synthesis.