What Is Chemical Proteomics Analysis
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Custom synthesis of diverse chemical probes, including ABPs, click-chemistry probes, and photoaffinity probes
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High-throughput workflows compatible with tissues, cultured cells, and biofluids
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Quantitative strategies supported: TMT, SILAC, and label-free approaches
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Deliverables include active protein profiling, differential expression analysis, and pathway enrichment results
Introduction: From Expression Levels to Functional States — A New Advancement in Proteomics
Proteomics traditionally focuses on profiling protein expression levels, thereby revealing changes in protein abundance under different conditions. However, this strategy often fails to capture the functional state of proteins — whether they are active or inactive, engaged in binding interactions or existing in a free form. To overcome this limitation, the field of Chemical Proteomics has emerged. By employing specialized chemical probes capable of targeting functionally active proteins and integrating high-resolution mass spectrometry, Chemical Proteomics enables precise mapping of protein functional states. It serves not only as a methodological approach, but also as a vital bridge connecting protein function, disease mechanisms, and drug discovery.
Core Principles of Chemical Proteomics
Chemical Proteomics is founded on the covalent labeling and selective enrichment of functionally active proteins, followed by mass spectrometry-based quantification to uncover protein subsets that are biologically active under specific physiological or pathological contexts.
This workflow typically involves the following key steps:
1. Design and labeling of chemical probes: Probes are designed to covalently bind to active proteins, enabling selective and precise target recognition.
2. Click chemistry or affinity-based enrichment: Target proteins are enriched using strategies such as biotinylation or fluorescent labeling.
3. Proteolysis and mass spectrometry analysis: Proteins are enzymatically digested into peptides, which are then analyzed using high-resolution mass spectrometry for identification and quantification.
4. Bioinformatics analysis: Active proteins are computationally identified and subjected to functional enrichment and pathway analysis.
Chemical Probes: The "Search Engine" of Chemical Proteomics
1. Three Key Modules of Chemical Probes
(1) Recognition unit: Specifically interacts with the active sites of target enzymes or functional proteins
(2) Reactive group: Forms covalent bonds with specific amino acid residues, ensuring stable and irreversible labeling
(3) Reporter tag: Functional groups such as biotin, fluorophores, or alkynes, used for downstream enrichment and detection
2. Representative Types of Chemical Probes
(1) Activity-Based Probes (ABPs): Designed for covalent labeling of enzyme active sites, commonly used for profiling serine hydrolases, cysteine proteases, and similar classes
(2) Click Probes: Facilitate modular tagging through bioorthogonal chemistry, enabling flexible expansion and customization
(3) Photoaffinity Probes: Employed to capture and study transient interactions between small molecules and proteins through UV-activated crosslinking
Applications and Future Prospects of Chemical Proteomics
1. Profiling Active Proteins
Active proteins can be selectively labeled using specific chemical probes and analyzed via mass spectrometry to generate comprehensive functional protein maps in cells, tissues, or disease models. This approach facilitates the identification of critical regulatory nodes.
2. Target Identification and Mechanistic Studies of Drug Action
Chemical probes can act as competitive ligands in co-incubation experiments with candidate drugs to assess target engagement. This strategy is a valuable tool for validating drug targets and elucidating mechanisms of action.
3. Real-Time Monitoring of Signaling Pathways
Chemical proteomics enables the dynamic monitoring of enzymatic activities of signaling molecules, thereby allowing the characterization of key regulatory elements within complex signaling networks.
Solutions by MtoZ Biolabs
Leveraging a robust chemical proteomics platform, MtoZ Biolabs offers comprehensive, end-to-end services encompassing custom probe synthesis, high-resolution mass spectrometry analysis, and expert bioinformatics interpretation:
Chemical proteomics marks a significant advancement in proteome research. Unlike traditional approaches that focus solely on protein presence, it emphasizes protein activity. By integrating chemical probes with mass spectrometry, this field is emerging as a vital link between functional biology and precision medicine. For researchers aiming to investigate protein activity states, validate targets, or explore molecular mechanisms, the solutions provided by MtoZ Biolabs offer a powerful and reliable platform for in-depth functional proteomics analysis.
MtoZ Biolabs, an integrated chromatography and mass spectrometry (MS) services provider.
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