Chemoproteomics Service

Chemoproteomics is a cutting-edge approach that comprehensively characterize the mode of action of drugs in drug discovery by integrating chemical biology and proteomics. Utilizing chemical probes, reactive compounds, or photoaffinity labeling techniques, chemoproteomics enables the identification of small-molecule targets, binding sites, and regulatory networks within complex biological systems. Core workflow of chemoproteomics includes activity-based protein profiling, covalent binding capture, and mass spectrometry analysis. Chemoproteomics stands out by focusing not only on the proteins themselves but also on how small molecules modulate protein functions through chemical bonds or non-covalent interactions, demonstrating significant potential, particularly in drug target discovery. Chemoproteomics addresses the limitations of traditional methods in drug target identification, offering a more efficient approach to understanding the mechanisms of action of compounds. First, it enables precise identification of a drug’s direct targets, avoiding non-specific interference and providing a foundation for drug optimization. Second, by identifying disease-associated proteins and their regulatory molecules, chemoproteomics facilitates the discovery of novel biomarkers, accelerating advancements in precision medicine. Additionally, chemoproteomics offers new solutions for studying orphan receptors and proteins with unknown functions, unveiling their potential roles and molecular mechanisms. This analytical approach not only advances fundamental research but also provides innovative insights for clinical therapies, profoundly impacting drug development, disease mechanism studies, and personalized medicine.

 



Chen, X. et al. Proteomics. 2017. 

Figure 1. Workflow of ABPP

 

Service at MtoZ Biolabs

MtoZ Biolabs, an integrated Chromatography and Mass Spectrometry (MS) Services Provider, provides advanced proteomics, metabolomics, and biopharmaceutical analysis services to researchers in biochemistry, biotechnology, and biopharmaceutical fields. Our ultimate aim is to provide more rapid, high-throughput, and cost-effective analysis, with exceptional data quality and minimal sample consumption. MtoZ Biolabs provides advanced chemoproteomics services that enable precise identification of protein targets, interaction sites, and their functional mechanisms. Our service allows for a systematic understanding of how small molecules regulate protein functions, offering robust technical support for drug development, disease mechanism studies, and precision medicine. Our chemoproteomics services include probe-based chemoproteomics (ABPP) and probe-free chemoproteomics (CETSA/TPP, DARTS, SPROX, etc.), making it well-suited for identifying drug targets, studying how post-translational modifications (PTMs) regulate protein functions, and developing novel biomarkers. If you have customized requirements or are interested in our services, please feel free to contact us.

 



Gao, Y. et al. Adv Sci (Weinh). 2024.

Figure 2. Schematic Diagram of Probe-Free Chemoproteomics Approaches

 

Service Advantages

Advantages of MtoZ Biolabs chemoproteomics service:  

1. Diverse Technology Platforms  

MtoZ Biolabs offers a wide range of chemoproteomics solutions, including probe-based chemoproteomics and probe-free approaches. Our chemoproteomics services are tailored to address the specific requirements of different protein families, such as membrane proteins, low-abundance proteins, and orphan receptors, ensuring comprehensive coverage of various protein types and functions.  

 

2. High Sensitivity and Specificity  

Leveraging high-resolution mass spectrometry platforms (e.g., Orbitrap and Q Exactive HF) alongside advanced sample enrichment and separation techniques, we precisely identify low-abundance target proteins. By optimizing probe design and suppressing background noise, we enhance detection specificity, delivering high-quality target identification results.  

 

3. Efficient Data Processing and Target Validation Support  

With a professional bioinformatics team and advanced data analysis tools, we efficiently differentiate specific targets from non-specific binding proteins. Additionally, our chemoproteomics service provides functional validation support for candidate targets, enabling clients to confirm targets quickly, save research time, and reduce the challenges of target deconvolution.  

 

Case Study

1. Large-Scale Chemoproteomics Expedites Ligand Discovery and Predicts Ligand Behavior in Cells

Chemical modulation of protein function is an important experimental approach to elucidate biological mechanisms and is the most commonly used strategy for treating human diseases. However, approximately 80% of the human proteome lacks annotated small molecule ligands, thus leaving many proteins, including validated disease targets, out of reach for mechanistic elucidation and therapeutic innovation. To close this gap, unbiased approaches are urgently needed to advance ligand discovery. We set out to determine the proteome-wide binding preferences of more than 400 small molecule fragments through a chemoproteomics strategy based on intact cell processing. With this data, we aim to (i) identify hundreds of fragment-protein interactions and advance selected fragments to cellular active ligands, (ii) develop models using machine learning (ML) binary classifiers to predict small molecule behavior in natural biological systems, and (iii) build an interactive open-source interface to support extensive exploration of the data and all predictive models. Our large-scale chemoproteomics study identified hundreds of fragment-protein interactions that are primed for future exploration and chemical optimization. Furthermore, the researchers found that the generated data is amenable to ML-based models that enable them to predict how chemicals interact with the native proteome in intact cells by using their chemical structures as input. To maximize practical usefulness to the scientific community, all interactomes, enrichment tools, and ML models have been made publicly available for exploration via a web-based application. Together, these data and tools form a resource for interpreting fragment binding data and accelerating ligand discovery efforts.

 



Offensperger, F. et al. Science. 2024.

Figure 3. Schematic Representation of the Ligand Discovery Approach

 

2. Chemoproteomics Reveals Microbiota-Derived Aromatic Monoamine Agonists for GPRC5A

The microbiota produces a variety of metabolites that regulate host physiology and disease, but their protein targets and mechanisms of action remain incompletely elucidated. To address this challenge, researchers explored microbiota-derived indole metabolites and developed photoaffinity chemical probes for proteomics studies. They identified numerous potential indole metabolite-interacting proteins, including metabolic enzymes, transporters, immune sensors, and G protein-coupled receptors (GPCRs). Notably, researchers discovered that aromatic monoamines can bind to the orphan receptor GPRC5A and stimulate β-arrestin recruitment. Metabolomic and functional analyses further revealed microbiota species expressing specific amino acid decarboxylases that produce aromatic monoamine agonists for GPRC5A-β-arrestin recruitment. their analysis of synthetic aromatic monoamine derivatives identified 7-fluorotryptamine as a more potent GPRC5A agonist. These findings highlight the utility of chemoproteomics in identifying microbiota metabolite-interacting proteins and in developing small-molecule agonists for orphan receptors.

 



Zhao, X. et al. Nat Chem Biol. 2023.

Figure 4. Chemoproteomic Analysis of IAA-Interacting Proteins in Mammalian Cells

 

Applications

1. Drug Discovery and Development: Chemoproteomics aids in elucidating the targets of candidate drugs, thereby accelerating the drug development process.  

 

2. Biomarker Discovery: Through target deconvolution, chemoproteomics identifies disease-associated proteins, providing novel biomarkers for precision medicine.  

 

3. Research on Proteins with Unknown Functions: For orphan receptors and proteins with unknown functions, chemoproteomics can reveal their potential ligands or functional mechanisms.

 

FAQ

Q1: How can it be used to identify and validate low abundance protein targets in complex biological samples effectively?

Answer: Chemoproteomics identifies and validates low-abundance protein targets by leveraging highly specific chemical probes and advanced mass spectrometry techniques. Probe-based approaches, such as activity-based protein profiling (ABPP) or photoaffinity labeling, capture target proteins even in complex samples by forming covalent bonds or photo-induced interactions. High-resolution mass spectrometry platforms, like Orbitrap, enable precise detection of low-abundance proteins by maximizing sensitivity and reducing background noise. Additionally, enrichment techniques isolate target proteins for focused analysis, ensuring accurate identification. Bioinformatics tools further validate targets by distinguishing specific interactions from non-specific binding, while follow-up functional assays confirm the biological relevance. Our chemoproteomics service can integrate these methods to overcome the challenges of low-abundance protein detection and validation.

 

Deliverables

1. Comprehensive Experimental Details

2. Materials, Instruments, and Methods

3. Relevant Liquid Chromatography and Mass Spectrometry Parameters

4. The Detailed Information of Chemoproteomics

5. Mass Spectrometry Image

6. Raw Data