Chemical Proteomics Analysis Service

Chemical proteomics, as an important branch of proteomics, integrates methods used in synthetic chemistry, cell biology, and mass spectrometry. It aims to design small molecule (SM) probes to elucidate the mode of action of SMs and the function of protein in drug discovery. Within the context of natural products, chemical proteomics can be used to identify the protein binding to or targets of SMs in living cells. Chemical proteomics consists of two key steps: (1) probe design and synthesis; (2) target capture and protein identification. To date, four different types of probes have been developed to screen for SM targets with various structures; after targeting, there are also various protein identification methods suitable for different scenarios. Chemical proteomics provides a range of novel methods for target deconvolution, the discovery of drug response biomarkers and analysis of disease pathway in preclinical target validation. It has been widely used in pharmacology to identify the target of and study the mechanism of action of drug.

 

MtoZ Biolabs utilizes a high-resolution mass spectrometry platform to develop and validate cutting-edge chemical proteomics technology, which can be used in numerous fields such as biomarker research, drug and target discovery, pathway modeling, and action mechanism research, aiming to provide clients with high-quality and comprehensive target deconvolution service. We offer a variety of methods to identify and validate new drug targets to meet diverse needs.

 

Designing and synthesizing probes are the initial and critical steps in the target recognition process of chemical proteomics. MtoZ Biolabs offers four common types of probes, including: (1) Immobilized probes: biologically active natural products are covalently fixed on biocompatible inert resins (such as agarose and magnetic beads), serving as bait for screening target proteins in active proteome; (2) Activity-based probes (ABP): considering the activity of drug molecules, ABP can interact with proteins in active proteome before enrichment, and can even penetrate cell membranes to bind with target proteins in living cells, which  reflectes potential drug-target interactions in cells; (3) Click chemistry probes: such probes are covalently linked to affinity tags (biotin-azides, biotin-cyclopropenes) or fluorescent tags (rhodamine-azides, FITC-azides) through biorthogonal click reactions with their complements (azides, alkynes, etc.), which can be used for subsequent enrichment and target identification; (4) Photoaffinity probes: photoaffinity probes consist of a click chemistry probe scaffold and a photoaffinity group used to fix the probe to the target upon binding. The group can produce highly reactive radicals under specific wavelength light to promote covalent binding of the active molecule with its target.

 

For some natural products whose suitable modification sites is lacking or whose activity is affected by modification, MtoZ Biolabs provides non-labeled chemical proteomics methods based on drug affinity responsive target stability (DARTS) and thermal proteome profiling (TPP). DARTS protect target proteins from proteolytic enzyme through interactions with SMs. Initially, cell lysates are divided into aliquots and each aliquot is treated with target compounds, controls or inactive analogs, followed by limited proteolysis for the proteins in the cell lysates. Then samples are separated by SDS-PAGE and stained to identify SM-protein complex tolerant of proteolysis, and finally, MS is used to identify targeted proteins.

 

MtoZ Biolabs possess comprehensive chemical proteomics solutions composed of experimental design, sample preparation, probe synthesis, target identification, and data analysis, offering a one-stop service to meet your needs in drug development and biomarker research, drug and target discovery, pathway modeling, and drug action studies. With our comprehensive solutions, you can save time and costs in search of drug candidates, and can optimize drug development and discovery with high success rate. Welcome your consult for more detailed information!

 

Service at MtoZ Biolabs

1. Experimental Procedures

2. Relevant Mass Spectrometry Parameters

3. Detailed Chemical Proteomics Information

4. Mass Spectrometry Images

5. Raw Data