(S,R,S)-AHPC-Me-C10-NH2 hydrochloride

Background Introduction

(S,R,S)-AHPC-Me-C10-NH2 hydrochloride is a high-purity E3 ligase ligand-linker conjugate derived from the AHPC scaffold. It is engineered for advanced PROTAC (Proteolysis Targeting Chimera) and targeted protein degradation research, offering a versatile platform to generate potent bifunctional molecules for selective protein knockdown.

Mechanism

The mechanism of (S,R,S)-AHPC-Me-C10-NH2 hydrochloride centers on its dual functionality. The AHPC moiety selectively binds to the von Hippel-Lindau (VHL) E3 ubiquitin ligase. The terminal amine attached via a C10 alkyl linker enables facile conjugation with various protein-targeting ligands. Once incorporated into a PROTAC molecule, the ligand bridges the VHL E3 ligase to a target protein, facilitating ubiquitination and subsequent proteasomal degradation of the target. This approach allows for precise post-translational control of protein levels within the cell.

Applications

(S,R,S)-AHPC-Me-C10-NH2 hydrochloride is widely used in designing custom PROTACs for chemical biology and drug discovery research. Its long, flexible linker enhances the formation of effective ternary complexes between E3 ligase, PROTAC, and target protein. Researchers employ it to investigate protein function, validate drug targets, and explore new modalities for therapeutic protein degradation in fields such as oncology, neurodegeneration, and immunology. This reagent is also valuable in developing next-generation protein degraders and optimizing linker designs for improved potency and selectivity.

• Extended C10 linker offers optimal spatial flexibility for efficient PROTAC assembly and improved cellular permeability.
• Designed for VHL E3 ligase recruitment, ensuring potent and selective target protein degradation in PROTAC applications.

(S,R,S)-AHPC-Me-C10-NH2 hydrochloride serves as a versatile E3 Ligase Ligand-Linker Conjugate in the realm of PROTACs, facilitating targeted protein degradation by effectively bridging the E3 ligase and the target protein. The following provides a detailed description of this molecule, highlighting the linker, ligand, and selection of target protein ligands.

Linker: The linker in this molecule is a medium-length C10 chain, offering a balance between flexibility and rigidity, which is crucial for optimal spatial orientation between the ligase and target protein. It is non-cleavable, ensuring stable conjugation and effective degradation of the target protein.

Ligand: The ligand component is derived from AHPC, a potent and selective E3 ligase ligand. Its stereochemical configuration (S,R,S) enhances binding affinity and specificity, ensuring efficient recruitment of the E3 ligase to the target protein complex.

Reactive Site: The reactive site features an amine group (-NH2) that facilitates coupling with the target protein ligand. Recommended reaction types include amide bond formation or reductive amination, allowing for stable and specific conjugation to the target protein warhead.

Recommended Target Protein Ligand: The compatible warhead for this molecule is typically an electrophilic group that can form a covalent bond with nucleophilic residues on the target protein. This approach ensures robust and irreversible binding, making it suitable for applications in studying protein function and validating therapeutic targets in preclinical research.