Application of Chemical Proteomics Methods in the Identification of Natural Drug Targets: A Review of Probe Synthesis, Target Capture, and Protein Identification Techniques
Abstract and Introduction
Accurate identification of drug targets is a key step in modern drug development. Due to their structural complexity and diverse mechanisms of action, identifying targets for natural drugs has always faced significant challenges. As an emerging frontier technology in recent years, chemical proteomics combines chemical probes with high-throughput protein analysis techniques to provide systematic solutions for research on natural drug targets. This article systematically elaborates on the application progress of chemical proteomics technologies in identifying natural drug targets based on a review published in the journal 'Signal Transduction and Targeted Therapy'.
The core concept behind chemical proteomics methods lies in constructing molecular probes that can specifically recognize target proteins associated with drugs. These probes must meet three basic requirements simultaneously: maintaining the biological activity of the original drug, possessing detectable reporter groups, and sustaining stable interactions with target proteins. Compared to traditional target identification methods, this technology offers significant advantages such as high throughput, strong specificity, and capability for in situ detection—making it particularly suitable for studying complex natural products like artemisinin.
Classification and Technical Principles of Chemical Proteomics Methods
Based on differences in workflow and probe design strategies, current mainstream chemical proteomics methods can be divided into two main categories: Activity-Based Protein Profiling (ABPP) techniques focused on active protein analysis; and Compound-Centric Chemical Proteomics (CCCP), which centers around compounds. Although these two technical routes differ slightly regarding specific operational details, they follow similar fundamental experimental processes.
The ABPP technique first requires structural modification of active drug molecules by introducing specific reporter groups to form probe molecules that can specifically bind to active sites on target proteins through subsequent enrichment followed by mass spectrometry analysis for target identification. The advantage here is its ability to directly reflect biological activity characteristics related to drugs—especially suited for enzyme-target studies. Conversely, CCCP employs a strategy where active molecules are fixed onto solid matrices using affinity capture from complex protein mixtures to screen potential targets; this method is more appropriate for studying weak or transient interaction systems involving target proteins.
Advances in Probe Design and Synthesis Technologies
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