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Solvent-induced proteome profiling for proteomic quantitation and target discovery of small molecular drugs
Authors:Chengli Yu  Xiuzhen Chen  Weiwei Xu  Simin Li  Qian Chai  Yinan Zhang
Affiliation:Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
Abstract:Target identification by modification-free proteomic approaches can potentially reveal the pharmacological mechanism of small molecular compounds. By combining the recent solvent-induced protein precipitation (SIP) method with TMT-labeling quantitative proteomics, we propose solvent-induced proteome profiling (SIPP) approach to identify small molecule–protein interactions. The SIPP approach enables to depict denaturation curves of the target protein by varying concentrations of organic solvents to induce unfolding and precipitation of the cellular proteome. By using this approach, we have successfully identified the known targets of market drugs and natural products and extended the proteome information of SIP for target identification.
Keywords:mass spectrometry  methotrexate  solvent-induced proteome profiling  staurosporine  target identification
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