(2S,4R)-1-[(2S)-2-acetamido-3-methylbutanoyl]-4-hydroxy-N-[(1S)-3-(methylamino)-3-oxo-1-phenylpropyl]pyrrolidine-2-carboxamide

Background Introduction

(2S,4R)-1-[(2S)-2-acetamido-3-methylbutanoyl]-4-hydroxy-N-[(1S)-3-(methylamino)-3-oxo-1-phenylpropyl]pyrrolidine-2-carboxamide is a synthetic peptide-based ligand specifically engineered for binding to the von Hippel-Lindau (VHL) E3 ubiquitin ligase. VHL ligands play a critical role in the design and synthesis of PROTAC (Proteolysis Targeting Chimera) molecules, enabling targeted protein degradation and helping researchers develop next-generation therapies for cancer, neurodegeneration, and other diseases. This peptide VHL ligand features high binding affinity and selectivity, providing a reliable building block for bifunctional degrader molecules.

Mechanism

This VHL ligand mimics natural HIF-1α peptide motifs, enabling high-affinity binding to the VHL E3 ubiquitin ligase complex (CRL2VHL). When integrated into a PROTAC molecule, the ligand brings VHL in close proximity to a target protein, which is simultaneously engaged by a target ligand. This proximity triggers ubiquitination of the target protein, leading to its recognition and subsequent degradation by the 26S proteasome. The specificity and high affinity of the VHL ligand are essential for efficient and selective targeted protein degradation.

Applications

(2S,4R)-1-[(2S)-2-acetamido-3-methylbutanoyl]-4-hydroxy-N-[(1S)-3-(methylamino)-3-oxo-1-phenylpropyl]pyrrolidine-2-carboxamide is widely used in drug discovery programs employing VHL-recruiting PROTAC platforms. Its optimized peptide structure supports robust conjugation to a variety of linkers and target ligands, enabling rapid synthesis and screening of novel PROTACs. Key applications include:

• Synthesis of VHL-based PROTAC molecules for targeted degradation of disease-associated proteins
• Investigation of VHL-mediated ubiquitination pathways in cell biology and chemical biology research
• Structure-activity relationship (SAR) studies aimed at optimizing VHL-ligand affinity and selectivity
• Development of chemical probes and tool molecules for functional proteomics and target validation

• High-purity compound verified by HPLC, NMR, and LC-MS
• Consistent batch-to-batch reproducibility with complete QC documentation
• Supplied with COA, MSDS, and analytical data for traceability
• Reliable global shipping with stability-guaranteed packaging
• Dedicated technical support and optional custom synthesis service
• Demonstrates strong binding affinity to CRBN, VHL, or other E3 ligases
• Enables stable E3 ligase recruitment for targeted protein degradation
• Optimized for selective VHL E3 ligase recruitment, enhancing targeted protein degradation in PROTAC applications.
• High purity and well-characterized structure enable consistent and reproducible results in drug discovery and chemical biology research.