(S,R,S)-AHPC-C2-NH2

Background Introduction

(S,R,S)-AHPC-C2-NH2 is a specialized E3 ligase ligand-linker conjugate designed for use in targeted protein degradation research. It is based on the (S,R,S)-AHPC scaffold, a potent ligand for the Von Hippel-Lindau (VHL) E3 ubiquitin ligase. The C2 linker and terminal amine functionality (NH2) allow for easy conjugation to various warheads or payloads, making it a critical building block for PROTAC (Proteolysis Targeting Chimera) molecule synthesis. Utilizing (S,R,S)-AHPC-C2-NH2 can contribute significantly to the development of novel therapeutics targeting previously 'undruggable' proteins.

Mechanism

The mechanism of (S,R,S)-AHPC-C2-NH2 involves selective recruitment of the VHL E3 ligase, one component of the cell’s ubiquitin-proteasome system. When incorporated into a PROTAC construct, the AHPC moiety binds VHL, while the other end of the molecule is covalently attached to a ligand that targets a protein of interest. The C2 linker provides an optimal spatial arrangement between the two functional groups. Upon ternary complex formation, the recruited E3 ligase ubiquitinates the target protein, marking it for degradation by the 26S proteasome. This allows for rapid and selective depletion of pathogenic proteins within cells.

Applications

(S,R,S)-AHPC-C2-NH2 is widely used in the field of chemical biology and drug discovery for constructing VHL-based PROTACs. Its versatile amine-terminated linker facilitates conjugation with various targeting ligands, enabling the creation of bifunctional molecules that degrade oncogenic, neurodegenerative, or inflammatory proteins. Applications include target validation, mechanism-of-action studies, and the development of next-generation small-molecule therapeutics. Additionally, this ligand-linker conjugate empowers researchers to explore new targets and advance the design of proteolysis-targeting therapeutics with improved selectivity and efficacy.

• High-affinity VHL ligand enables effective ubiquitin E3 ligase recruitment for targeted protein degradation.
• C2 linker with terminal amine functional group facilitates flexible and efficient PROTAC synthesis for customized applications.