(S,R,S)-AHPC-C3-NH2

Background Introduction

(S,R,S)-AHPC-C3-NH2 is a specialized bifunctional molecule designed for use in targeted protein degradation research, particularly in the development of PROTACs (Proteolysis Targeting Chimeras). This compound consists of the potent VHL (von Hippel-Lindau) E3 ligase ligand, (S,R,S)-AHPC, tethered to an amino-terminated C3 linker, enabling facile conjugation with target-binding ligands. The high specificity and optimized linker length make it a valuable building block for generating novel PROTACs compatible with a variety of protein targets.

Mechanism

The mechanism of (S,R,S)-AHPC-C3-NH2 centers on targeted protein degradation via the ubiquitin-proteasome system. In PROTAC design, this linker conjugate acts as the E3 ligase-recruiting component. Upon conjugation with a suitable ligand for the protein of interest, the resulting PROTAC molecule bridges the target protein to the VHL E3 ligase. This proximity promotes the ubiquitination of the target, effectively marking it for degradation by the cellular proteasome machinery. The C3 linker provides optimal spacing and flexibility for efficient formation of the ternary complex, facilitating selective and rapid target protein elimination.

Applications

(S,R,S)-AHPC-C3-NH2 is widely applied in medicinal chemistry, drug discovery, and chemical biology research. Its primary use is as a modular component in the synthesis of VHL-based PROTACs for targeted protein degradation. Researchers utilize this linker conjugate to design and optimize PROTACs aimed at diverse disease-relevant proteins, enabling the study of protein function, target validation, and development of first-in-class therapeutic candidates. Additionally, (S,R,S)-AHPC-C3-NH2 can serve in the generation of tool compounds for probing biological pathways and proteostasis mechanisms.