DARTS (Drug Affinity Responsive Target Stability) is a novel technique developed based on the reduced sensitivity of target proteins to protease degradation caused by the binding of small molecule drugs to their target proteins. This technique can be used for drug screening and target identification without chemical modification of the compound, as well as not dependent on drug activity.
Small molecules have been used as drugs for thousands of years, and they have played an important role in social and economic development, in addition to relieving the suffering caused by diseases and improving the population's health. Mechanistically, small-molecule drugs penetrate cell membranes and bind to specific targets, hence affecting the functions of cells and tissues as well as manifesting particular therapeutic or preventive roles. Traditionally, the discovery and identification of drug targets often apply physical or chemical means such as affinity chromatography, isotope tracing, UV, and fluorescence spectroscopy. With the increasing drug discovery requirements, new drug development and drug target discovery confront various challenges, and certain traditional drug screening methods and target identification techniques are in need of innovation.
In recent years, with the application and development of various technologies such as genomics, proteomics, and bioinformatics, new technologies and methods of high throughput and high efficiency have emerged, and the DARTS technology is one of these novel technologies based on proteomics for small molecule drug screening and target discovering, and was first reported in 2009.
Methods of DARTS
DARTS experiments require specific strategies to detect the effect of enzymatic digestion, commonly used methods such as SDS-PAGE, gum staining techniques (e.g., Thomas Brilliant Blue staining), etc. In addition, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and mass spectrometry (LC-MS/MS) can also be used to detect the differences in enzymatic digestion between the treated group and the control group by comparison and further discover the drug target candidates for subsequent experiments. The DARTS technique has been widely used due to its simple and time-saving operations. Our researchers have mastered these practices to help you accurately analyze small molecule drug targets.
Our DARTS Services
As a specialized Molecular Interaction CRO, Creative Proteomics has provided analytical services regarding the binding of small molecule drugs to their target proteins for the pharmaceutical industry and academic/nonprofit researchers using the patented DARTS technology.
Applications of DARTS Technology
DARTS can provide (1) unbiased proteome-wide drug target identification using the latest proteomics and mass spectrometry technologies; (2) specific protein target binding tests for your drug of interest; (3) drug screening for the "undruggable" therapeutic targets.
Workflow of DARTS assay
Advantages
- Flexible, cost-effective, and time-saving target identification services
- Detection of molecular bindings, including weak small molecule-protein interactions
- No additional modifications or tagging of small molecule compounds required
- Sophisticated bioinformatics analysis of complete results
References
- Sun J, Prabhu N, Tang J, et al. Recent advances in proteome-wide label-free target deconvolution for bioactive small molecules[J]. Medicinal Research Reviews.
- Zhang X, Wang Q, Li Y, et al. Solvent-Induced Protein Precipitation for Drug Target Discovery on the Proteomic Scale[J]. Analytical Chemistry, 2020, 92(1):1363-1371.