Establishment of the methodology for target identification of bioactive natural products based on the chemical genomics

基于化学基因组学的生物活性天然产物靶点鉴定方法学的建立

• 批准号: 22659022
• 负责人: ARAI Masayoshi
• 金额: $ 1.98万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22659022/
• 关键词: ケミカルジェノミクス; ケミカルバイオロジー; 生物活性物質; 標的分子; ケミカルゲノミックス

With the transformants of HeLa cells with cDNA library or the next-generation sequencer, we tried establishment of the general methodology to clarify the target molecules of the bioactive natural products that acts on the eukaryotes such as an animal cells. Using topoisomerase I inhibitor of camptothecin as a model compound, we succeeded in the establishment of the methods, which selects a camptothecin-resistant HeLa cell from the transformants of HeLa cells that over-expressed cDNA randomly, and analyzes the cDNA introduced from the camptothecin-resistant HeLa cell. We also succeeded in the preparation of spontaneous resistant HeLa cells against camptothecin for exhaustively analyzing genetic mutation using a next-generation sequencer.

利用带cDNA文库的HeLa细胞转化体或下一代测序仪，我们尝试建立一般的方法来阐明作用于真核生物（如动物细胞）的生物活性天然产物的靶分子。我们以喜树碱拓扑异构酶I抑制剂为模型化合物，成功建立了从过表达cDNA的HeLa细胞转化体中随机筛选喜树碱耐药HeLa细胞的方法，并对从喜树碱耐药HeLa细胞导入的cDNA进行分析。我们还成功地制备了自发抗喜树碱的HeLa细胞，用于使用下一代测序仪详尽地分析基因突变。

项目成果

Action-Mechanism of Trichoderin A, an Anti-dormant Mycobacterial Aminolipopeptide from Marine Sponge-Derived Trichoderma sp.

• DOI: 10.1248/bpb.34.1287
• 发表时间: 2011-08-01
• 期刊: BIOLOGICAL & PHARMACEUTICAL BULLETIN
• 影响因子: 2
• 作者: Pruksakorn, Patamaporn;Arai, Masayoshi;Kobayashi, Motomasa
• 通讯作者: Kobayashi, Motomasa

低酸素環境選択的がん細胞増殖阻害物質furospinosulin-1の作用メカニズム解析

缺氧环境下选择性癌细胞增殖抑制剂呋喃肌苷蛋白-1的作用机制分析

• 发表时间: 2013
• 作者: Hirotada Mori;荒井 雅吉
• 通讯作者: 荒井 雅吉