Discovery of novel RNA G-quadruplex ligands from a chemical library

• Project/Area Number: 15K17883
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bio-related chemistry
• Research Institution: Kumamoto University (2017); Kyoto University (2015-2016)
• Principal Investigator: KATSUDA Yousuke 熊本大学, 大学院先端科学研究部(工), 助教 (50632460)
• Co-Investigator(Renkei-kenkyūsha): UESUGI Motonari 京都大学, 化学研究所, 教授 (10402926) ; SATO Shin-ichi 京都大学, 化学研究所, 准教授 (70534478)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: RNA G-quadrupelx / translation / screening / RNA G-quadruplex / Translation / スクリーニング / タンパク質翻訳反応制御 / 核酸

Outline of Final Research Achievements

The highlights of this study are: (i) the chemical library screening allowed us to discover a highly-selective RNA G-quadruplex stabilizer with a new chemical scaffold and physical property, (ii) the protein expression level of endogenous NRAS, a well-known proto-oncogene, was down-regulated with the stabilizer in living cells for the first time, and (iii) the RNA G-quadruplex stabilizer enabled the detection of a previously unidentified RNA G-quadruplex in 5’-UTR of NRAS.

Research Products

• [Journal Article] A synthetic hybrid molecule for the selective removal of human pluripotent stem cells from cell mixtures. (2017)
  • Author(s): Mao, D., Ando, S., Sato, S., Qin, Y., Hirata, N., Katsuda, Y., Kawase, E., Kuo, T.F., Minami, I., Shiba, Y., Ueda, K., Nakatsuji, N., Uesugi, M.
  • Journal Title: Angew. Chem. Int. Ed. Volume: 56 Issue: 7 Pages: 1765-1770
  • DOI: 10.1002/anie.201610284
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A small molecule that represses translation of G-quadruplex-containing mRNA. (2016)
  • Author(s): Katsuda, Y., Sato, S., Asano, L., Morimura, Y., Furuta, T., Sugiyama, H., Hagihara, M., Uesugi, M.
  • Journal Title: J. Am. Chem. Soc. Volume: 138 Issue: 29 Pages: 9037-9040
  • DOI: 10.1021/jacs.6b04506
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] CRISPR／Cas９がもたらす薬物標的解析への恩恵 (2015)
  • Author(s): 勝田 陽介
  • Journal Title: ファルマシア Volume: 51 Pages: 459-459
  • NAID: 130007448193
• [Presentation] Exploration the RNA G-quadruplex using a small molecule (2017)
  • Author(s): Yousuke Katsuda, Shin-ichi Sato, Kenji Yatsuzuka, Motonari Uesugi
  • Organizer: 日本化学会 第97春季年会
  • Place of Presentation: 慶應義塾大学 日吉キャンパス
  • Year and Date: 2017-03-16
• [Presentation] Exploration of the RNA G-quadruplex using a small molecule (2017)
  • Author(s): Yousuke Katsuda, Shin-ichi Sato, Kenji Yatsuzuka, Motonari Uesugi
  • Organizer: 日本化学会春季年会
• [Presentation] Yousuke Katsuda, Shin-ichi Sato, Motonari Uesugi , Toshihiro Ihara (2017)
  • Author(s): RGB-1を用いたRNA G-quadruplexの網羅的な探索
  • Organizer: 日本ケミカルバイオロジー学会
• [Presentation] RNA G-quadruplex選択的化合物を用いた網羅的なRNA G-quadruplexの探索 (2016)
  • Author(s): 勝田 陽介・佐藤 慎一・萩原 正規・八塚 研治・上杉 志成
  • Organizer: 第10回バイオ関連シンポジウム
  • Place of Presentation: 石川県立音楽堂
  • Year and Date: 2016-09-07
• [Presentation] Discovering a Latent RNA G-quadruplex with a Small Molecule (2016)
  • Author(s): Yousuke Katsuda, Shin-ichi Sato, Tomoyuki Furuta, Masaki Hagihara, Motonari Uesugi
  • Organizer: 日本ケミカルバイオロジー学会 第11回年会
  • Place of Presentation: 京都テルサ
  • Year and Date: 2016-06-15
• [Presentation] RNA G-quadruplex-targeting translational inhibition using a small molecule (2016)
  • Author(s): Yousuke Katsuda, Shin-ichi Sato, Masaki Hagihara, Motonari Uesugi
  • Organizer: 日本化学会年会
  • Place of Presentation: 同志社大学 (京都府京田辺市)
  • Year and Date: 2016-03-25
• [Presentation] A screening method for RNA G-quadruplex stabilizers (2015)
  • Author(s): Yousuke Katsuda, Shin-ichi Sato, Motonari Uesugi
  • Organizer: PACIFICHEM
  • Place of Presentation: Honolulu (USA)
  • Year and Date: 2015-12-19
  • Int'l Joint Research
• [Presentation] RNA G-quadruplex選択的結合化合物を用いた翻訳阻害 (2015)
  • Author(s): 勝田陽介、佐藤慎一、古田智行、上杉志成
  • Organizer: 第9回バイオ関連シンポジウム
  • Place of Presentation: 熊本大学 (熊本県熊本市)
  • Year and Date: 2015-09-10
• [Presentation] The 6th International Symposium of Advanced Energy Science ～Towards the Realization of Zero-Emission Energy～ (2015)
  • Author(s): Yousuke Katsuda, Shin-ichi Sato, Eiji Nakata, Takashi Morii, Motonari Uesugi
  • Organizer: Development of a small molecule that has affinity to RNA G-quadruplex
  • Place of Presentation: 京都大学 (京都府宇治市)
  • Year and Date: 2015-09-02
  • Int'l Joint Research