Custom Molecular Glues Synthesis Service
- Nuclear Magnetic Resonance (NMR): Used to confirm the key hydrogen and carbon resonance points of the molecule to ensure the correct structure;
- Liquid Chromatography-Mass Spectrometry (LC-MS): Rapidly detects the molecular mass and assists in confirming the overall structural integrity;
- High-Performance Liquid Chromatography (HPLC): Measures the purity of the compound, ensuring >95% single component content.
Molecular glues are small molecules that induce new types of protein-protein interactions, thereby regulating the stability and function of specific target proteins. Unlike traditional small molecule inhibitors or agonists, molecular glues do not directly block or activate targets but instead promote "induced proximity" between two proteins that do not naturally interact. This interaction then leads to protein ubiquitination, degradation, or functional modulation. This unique mechanism offers significant potential in precision drug development, targeted protein degradation (TPD), and functional proteomics.
MtoZ Biolabs, with its deep expertise in targeted protein degradation and efficient organic synthesis capabilities, offers the Custom Molecular Glues Synthesis Service to support both scientific research and pharmaceutical development. This service is designed for teams involved in molecular glue development, helping clients rapidly obtain structurally defined, stable, and mechanism-validated small molecule glue candidates.
Services at MtoZ Biolabs
Our Custom Molecular Glues Synthesis Service combines structure-guided design and literature-based optimization strategies to build customized small molecule scaffolds. It focuses on synthesizing structurally defined, stable small molecules capable of inducing protein-protein interactions, helping clients advance their research in structural biology, functional mechanism studies, and targeted protein degradation. Our service includes:
1. Small Molecule Core Scaffold Screening and Structural Modification
Based on the structural characteristics of target proteins and E3 ubiquitin ligases (e.g., CRBN, VHL), we prioritize selecting core scaffolds with proven degradation activity from the literature or databases (e.g., phthalimide, sulfonamide). We then modify side chains or aromatic rings based on the surface charge, hydrophobicity, and steric configuration of the target protein to enhance the stability of the core scaffold within the ternary complex. This allows us to design scaffolds that possess both CRBN-binding ability and potential to induce target protein interaction.
2. Functional Group Conjugation Design
To improve the protein affinity and induction activity of the synthesized molecules, we introduce key functional groups onto the core scaffold. During this design process, molecular docking simulations or known ternary complex structures from literature are used to select favorable side-chain directions and substitution sites that enhance the stability of protein interaction interfaces.
3. Induced Protein Interface Formation Capability Assessment
After the initial design, we assess the potential of the designed molecules to induce protein interaction. This process involves combining known PDB structures, AlphaFold prediction models, and distance and angle analysis of ternary complexes to determine whether the modified molecule can physically interact with both E3 ligase and the target protein. If necessary, molecular dynamics (MD) simulations are used to assess conformational flexibility, and feasible candidates are selected for synthesis.
4. Organic Synthesis and Purification
Based on the confirmed target molecule structure, we adopt linear or modular synthesis strategies. Reactions such as amination, Suzuki coupling, acylation, and reductive amination are used. Throughout the synthesis process, each intermediate undergoes standard purification (column chromatography, liquid-liquid extraction, recrystallization, etc.) to ensure smooth downstream steps. The final product is purified using preparative HPLC to ensure it meets the required purity for structural biology and cell experiments.
5. Standard Structural Validation
All synthesized products undergo triple structural confirmation, including:
If necessary, we can also provide stability or solubility testing data for downstream cell-based assays or structural analysis.
Analysis Workflow
Service Advantages
1. Precision-Based Molecular Glue Design
We carefully consider the structural characteristics of both the E3 ligase and target protein in the design process, utilizing efficient structural analysis tools and literature research to optimize the core scaffold and functional group conjugation. This strategy significantly enhances the candidate molecules' potential for target induction, ternary complex formation, and protein degradation, ensuring that clients can effectively screen active molecular glues at the early stages of drug discovery.
2. Highly Customizable Modular
Our service is flexible and can be tailored to the client's specific needs. Whether for early-stage functional screening or late-stage structural optimization and validation, we provide a fully customized solution to meet various research requirements.
3. High-End Technology Platform
MtoZ Biolabs is equipped with industry-leading analysis platforms, such as the Thermo Fisher Q Exactive HF mass spectrometer and Nano-LC system, which can accurately perform molecular glue structural verification and quality detection. Additionally, our high-throughput equipment supports all stages of molecular design and functional validation, ensuring that each batch of molecular glue meets the required quality and activity for pharmaceutical research and scientific applications.
4. Rigorous Quality Control Standards
To ensure that each batch of products meets high-quality standards, we use multiple detection methods such as NMR, LC-MS, and HPLC to rigorously validate the structure and purity of the compounds. This ensures the reliability and consistency of the delivered samples for downstream research.
5. Experienced Technical Team
Our technical team consists of senior organic chemists, proteomics experts, and drug development consultants, with extensive backgrounds in molecular glue design, protein interaction mechanisms, and protein degradation pathways. This interdisciplinary expertise enables us to provide in-depth technical support and innovative solutions for complex drug discovery needs, whether for academic research or commercialization.
Applications
1. Development of candidate compounds for targeted protein degradation research
2. Screening and validation of new E3 ligase recruitment mechanisms
3. Construction of tool molecules for functional proteomics
4. Target validation and pharmacodynamics exploration in preclinical studies
5. Molecule development for ternary complex structure research
FAQ
Q1: Can you only synthesize the structure without functional testing?
A1: Yes. We offer structural synthesis and validation services, and whether to conduct functional testing is up to the client's decision.
Q2: How long does the synthesis process take?
A2: The synthesis process typically takes 3–6 weeks, depending on the complexity of the structure and optimization route.
Q3: Is the project confidential?
A3: Yes, MtoZ Biolabs strictly adheres to confidentiality agreements to ensure that client data and structures are not disclosed.
Deliverables
1. Synthesis of target compounds: Delivered in the form specified by the client (solid powder or solution), with purity ≥95%, suitable for biochemical/cell experiments.
2. Structural confirmation report: Includes 1H/13C NMR spectra, LC-MS spectra, used to confirm the molecular composition and chemical sites of the target structure.
3. Purity testing report: Provides HPLC chromatograms and purity percentages, ensuring the sample is suitable for structural biology or functional validation experiments.
4. Synthesis route and basic process information (optional): A brief explanation of the synthesis steps can be provided, subject to agreement.
5. Project summary report (if applicable): For projects involving multiple candidate molecules, we provide initial screening results, structural modification recommendations, and other technical summaries.
If you are looking for a trusted partner for custom molecular glue synthesis, MtoZ Biolabs offers professional and reliable technical support. We specialize in connecting molecular design with biological mechanisms, helping you advance protein degradation drug development and cutting-edge mechanism research. Feel free to contact us for project evaluation and custom service proposals!
How to order?
