(S,R,S)-AHPC-PEG1-NH2 hydrochloride

Background Introduction

(S,R,S)-AHPC-PEG1-NH2 hydrochloride is a versatile E3 ligase ligand-linker conjugate based on the AHPC (3-amino-2-hydroxy-4-phenylbutanoic acid) scaffold. It is designed to facilitate targeted protein degradation through the proteolysis targeting chimera (PROTAC) approach. The incorporation of a hydrophilic PEG1 linker and terminal amine functionality enables convenient conjugation to various target-binding ligands, making this compound an essential building block for rational PROTAC design.

Mechanism

(S,R,S)-AHPC-PEG1-NH2 hydrochloride operates as a cereblon (CRBN) E3 ligase ligand. When covalently linked via the PEG1 spacer to a ligand that binds a protein of interest, this bifunctional molecule induces the formation of a ternary complex between the target protein, the PROTAC, and the CRBN E3 ubiquitin ligase. Recruitment of CRBN leads to ubiquitination of the target protein, marking it for proteasomal degradation. The PEG1 linker introduces flexibility and hydrophilicity, potentially improving the pharmacokinetic and physicochemical properties of the resulting PROTAC.

Applications

This E3 ligase ligand-linker conjugate is widely used in the discovery and development of PROTAC molecules. (S,R,S)-AHPC-PEG1-NH2 hydrochloride enables researchers to efficiently synthesize novel PROTACs for targeted protein degradation studies, mechanism-of-action investigations, and drug discovery programs across oncology, neurodegenerative diseases, and immunology. Its modular design streamlines structure-activity relationship (SAR) studies and accelerates the optimization of PROTAC efficacy, selectivity, and drug-like properties.