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Comprehensive TCM molecular networking based on MS/MS in silico spectra with integration of virtual screening and affinity MS screening for discovering functional ligands from natural herbs

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Abstract

Accessing the rich source of compounds from natural herbs for use in the pharmaceutical industry using conventional bioassay-based screening platforms has low efficiency and is cost-prohibitive. In this study, we developed a new method involving traditional Chinese medicine (TCM) molecular networking and virtual screening coupled with affinity mass spectrometry (MN/VS-AM) for the efficient discovery of herb-derived ligands. The in silico MS/MS fragmentation database (ISDB) generated by molecular networking of TCM can rapidly identify compounds in complex herb extracts and perform compound activity mapping. Additionally, the pre-virtual screening conveniently includes candidate herbs with potential bioactivity, while affinity MS screening completely eliminates the requirement for a tedious pure compound preparation at the initial screening phase. After applying this approach, two types of compounds, isoamylene flavanonols and 20(s)-protopanoxadio saponins, which were confirmed to interact with the small GTPase of Ras, were successfully identified from a dozen anti-cancer TCM herbs. The results demonstrate that the modified screening strategy dramatically improved the accuracy and throughput sensitivity of ligand screening from herbal extracts.

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Acknowledgements

This research was supported by the International Cooperation and Exchange of the National Natural Science Foundation of China (No. 81761168039), the National Key Research and Development Program of China (No. 2018YFC1704800, 2018YFC1704805, 2018YFC1704500, 2018YFC1704505) and the National Natural Science Foundation of China (No. 81673616).

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Authors and Affiliations

  1. State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, China

    Zhihua Wang, Unchol Kim, Chuanjing Cheng, Wenbo Wu, Shuang Guo, Yuanyuan Hou & Gang Bai

  2. School of Chemistry and Chemical Engineering, Tianjin University of Technology, Xiqing Park, 391 Binshui Road, Tianjin, 300384, China

    Jinbiao Liu

  3. Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD, 4111, Australia

    Yunjiang Feng & Ronald J. Quinn

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  1. Zhihua Wang
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Wang, Z., Kim, U., Liu, J. et al. Comprehensive TCM molecular networking based on MS/MS in silico spectra with integration of virtual screening and affinity MS screening for discovering functional ligands from natural herbs. Anal Bioanal Chem 411, 5785–5797 (2019). https://doi.org/10.1007/s00216-019-01962-4

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