Identification of the Natural Product Rotihibin A as a TOR Kinase Signaling Inhibitor by Unbiased Transcriptional Profiling
| Autor: | Farnusch Kaschani, Yanlin Liu, Markus Kaiser, Julian Oeljeklaus, Erich Kombrink, Yan Xiong, Michael Ehrmann, Geronimo Heilmann, Markus Schlicht, Jasmin Schillinger, Vivek Halder, Jan H. Krahn, Barbara Kracher |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular Arabidopsis Gene Expression Computational biology 01 natural sciences Catalysis Transcriptome Small Molecule Libraries 03 medical and health sciences chemistry.chemical_compound Kinase signaling Profiling (information science) Protein Kinase Inhibitors Sirolimus Biological Products Natural product 010405 organic chemistry Gene Expression Profiling TOR Serine-Threonine Kinases Organic Chemistry General Chemistry 0104 chemical sciences TOR signaling Multicellular organism 030104 developmental biology chemistry Cell culture Mutation Natural Product Research Biologie Oligopeptides |
| Zdroj: | Chemistry (Weinheim an der Bergstrasse, Germany). 24(48) |
| ISSN: | 1521-3765 |
| Popis: | Bioactive natural products are important starting points for developing chemical tools for biological research. For elucidating their bioactivity profile, biological systems with concise complexity such as cell culture systems are frequently used, whereas unbiased investigations in more complex multicellular systems are only rarely explored. Here, we demonstrate with the natural product Rotihibin A and the plant research model system Arabidopsis thaliana that unbiased transcriptional profiling enables a rapid, label-free, and compound economic evaluation of a natural product's bioactivity profile in a complex multicellular organism. To this end, we established a chemical synthesis of Rotihibin A as well as that of structural analogues, followed by transcriptional profiling-guided identification and validation of Rotihibin A as a TOR signaling inhibitor (TOR=target of rapamycin). These findings illustrate that a combined approach of transcriptional profiling and natural product research may represent a technically simple approach to streamline the development of chemical tools from natural products even for biologically complex multicellular biological systems. |
| Databáze: | OpenAIRE |
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