VH 032-linker 5 is a high-purity E3 Ligase Ligand-Linker Conjugate specifically engineered for use in PROTAC (Proteolysis Targeting Chimera) drug discovery. This compound features the well-characterized VH 032 ligand, which selectively targets the von Hippel-Lindau (VHL) E3 ubiquitin ligase, conjugated to a versatile linker. VH 032-linker 5 acts as a foundational building block for developing custom PROTAC molecules by enabling researchers to connect the E3 ligase targeting warhead to various ligands that bind target proteins. This conjugate facilitates the recruitment and degradation of disease-related proteins via the ubiquitin-proteasome pathway, advancing targeted protein degradation research in oncology, neurodegeneration, and other areas. As an essential tool for medicinal chemistry and early-stage drug development, VH 032-linker 5 accelerates PROTAC library synthesis and SAR optimization. Ideal for researchers developing next-generation targeted protein degraders, this product ensures reliable performance, consistency, and ease of use in laboratory workflows.
Structure of 2172819-74-6
* For research and manufacturing use only. Not for human or clinical use.
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Background Introduction
VH 032-linker 5 is a specialized E3 ligase ligand-linker conjugate commonly used in the design and synthesis of PROTACs (Proteolysis Targeting Chimeras). VH032 is a well-characterized ligand that specifically binds to the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex, enabling targeted protein degradation applications. By integrating a suitable linker, VH 032-linker 5 allows for the flexible and efficient assembly of bifunctional small molecules in drug discovery and targeted protein degradation research.
Mechanism
The mechanism of VH 032-linker 5 involves two key components: the VH032 moiety, which selectively binds to the VHL E3 ligase, and the linker, which provides the necessary spatial arrangement for connecting the E3 ligase binding domain to a ligand that recognizes the protein of interest (POI). When incorporated into a PROTAC molecule, VH 032-linker 5 enables the PROTAC to recruit the VHL E3 ligase to the target protein. This proximity induces polyubiquitination of the target protein, marking it for recognition and degradation by the proteasome, resulting in efficient and selective removal of the POI from the cell.
Applications
VH 032-linker 5 is widely used in the development of PROTACs for basic and translational research, especially in oncology, neurodegenerative diseases, and immunology. Its application enables the generation of customized PROTAC molecules targeting a variety of disease-associated proteins, facilitating drug discovery and functional characterization studies. Researchers utilize VH 032-linker 5 as an essential synthetic building block for novel protein degradation-based therapeutics and chemical biology tools, significantly accelerating the identification and validation of next-generation drug targets.
The VH 032-linker 5 E3 Ligase Ligand-Linker Conjugate plays a pivotal role in the development of PROTACs by facilitating targeted protein degradation. This versatile molecule offers enhanced specificity and efficiency in targeting proteins for degradation, with the following sections providing a detailed description of the linker, ligand, and selection of target protein ligands.
Linker: The linker in VH 032-linker 5 is characterized by its moderate length, providing a balance between flexibility and rigidity. It is designed to be non-cleavable, ensuring the stability of the PROTAC complex during the degradation process, and enabling efficient ubiquitination of the target protein.
Ligand: The ligand in this molecule is a derivative of the VH 032 moiety, known for its high affinity and specificity towards the VHL E3 ligase. Its structural characteristics include a lipophilic core that enhances cell permeability and a polar surface that facilitates binding interactions.
Reactive Site: The reactive site of VH 032-linker 5 is designed to couple efficiently with the target protein ligand through amide bond formation. This site is optimized for reactions such as amidation or click chemistry, providing robust conjugation with minimal side reactions.
Recommended Target Protein Ligand: A suitable warhead for VH 032-linker 5 is a small molecule inhibitor with a reactive functional group such as an amine or azide. These warheads are advantageous for their ability to form stable covalent bonds with the reactive site, allowing precise targeting of disease-relevant proteins. Applications include the degradation of kinases and transcription factors, offering a powerful tool for probing protein function in cellular studies.
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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