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Novel screenings for unmet medical needs with innovative new natural product derived compounds

Research Project

Project/Area Number 16H05346
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Infectious disease medicine
Research InstitutionTohoku University

Principal Investigator

Kodama Eiichi  東北大学, 災害科学国際研究所, 教授 (50271151)

Co-Investigator(Kenkyū-buntansha) 大島 吉輝  東北大学, 医学系研究科, 特任教授(客員) (00111302)
浅井 禎吾  東京大学, 大学院総合文化研究科, 准教授 (60572310)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2016: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords感染症 / ウイルス / 薬学 / 化学合成 / 天然物
Outline of Final Research Achievements

In the project, we have successfully established unique and divergent chemical libraries with innovative natural products under up-regulation of the synthetic enzymes and/or pathways of plants or microbes by various anti-silencing agents. Further chemical modifications have been applied to the isolated products and determined chemical structures with nuclear magnetic resonance analysis. In addition, we have also established several novel screening methods for unmet medical needs. Some compounds show new biological activities, such as anti-osteoporosis, anti-cancers associated with virus infections, and anti-viruses. These valuable achievements were published and presented in scientific meetings elsewhere. Our innovative libraries and novel screening systems based on chemical biology may contribute to rational drug designs and developments.

Academic Significance and Societal Importance of the Research Achievements

本研究により、近年、枯渇しつつある天然物由来新規化合物の効率的な取得を可能としただけでなく、化学修飾を加えることで飛躍的に多様性を有するライブラリーを既存法と比べ簡便かつ短時間に構築できることを明らかとした。希少疾患も含めたアンメットメディカルニーズに対応する新規化合物評価系を複数構築し、骨粗しょう症とウイルス発がんを抑制しうる天然物由来のヒットを見出したことから、我々のライブラリーの有用性を確認した。社会的には、少子化・高齢化に伴う疾患の複雑性に対応する薬剤開発の一助となったと思われる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (23 results)

All 2019 2018 2017 2016

All Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (14 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Use of plant hormones to activate silent polyketide biosynthetic pathways in Arthrinium sacchari, a fungus isolated from a spider2019

    • Author(s)
      Yohei Morishita, Yusuke Okazaki, Yi Yi Luo, Jun Nunoki, Tohru Taniguchi, Yoshiteru Oshima, Teigo Asai
    • Journal Title

      Org. Biomol. Chem.

      Volume: 17 Issue: 4 Pages: 780-784

    • DOI

      10.1039/c8ob02837k

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of human immunodeficiency virus type-1 Gag-TSG101 interaction inhibitors by high-throughput screening2018

    • Author(s)
      Lowela Siarot, Nopporn Chutiwitoonchai, Hirotaka Sato, Hao Chang, Hironori Sato, Masayuki,Fujino,Tsutomu Murakami,Toshihiro Aono, Eiichi Kodama, Kazumichi Kuroda, Masami Takei, Yoko Aida
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 503 Issue: 4 Pages: 2970-2976

    • DOI

      10.1016/j.bbrc.2018.08.079

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Construction of a Meroterpenoid‐Like Compounds Library Based on Diversity‐Enhanced Extracts2018

    • Author(s)
      Kikuchi Haruhisa、Kawai Kosuke、Nakashiro Yota、Yonezawa Takayuki、Kawaji Kumi、Kodama Eiichi. N.、Oshima Yoshiteru
    • Journal Title

      Chemistry- A European Journal

      Volume: 25 Issue: 4 Pages: 1106-1112

    • DOI

      10.1002/chem.201805417

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Cinnamon-Derived Procyanidin.Compound Displays Anti-HIV-1 Activity by Blocking Heparan Sulfate- and Co-Receptor- Binding Sites on gp120 and Reverses T Cell Exhaustion via Impeding Tim-3 and PD-1 Upregulation2016

    • Author(s)
      Connell BJ, Chang SY, Prakash E, Yousfi R, Mohan V, Posch W, Wilflingseder D, Moog C, Kodama EN, Clayette P, Lortat-Jacob H.
    • Journal Title

      PLoS One.

      Volume: 2 Issue: 10 Pages: e0165386-e0165386

    • DOI

      10.1371/journal.pone.0165386

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural basis of HIV inhibition by translocation-defective RT inhibitor 4'-ethynyl-2-fluoro-2'-deoxyadenosine(EFdA).2016

    • Author(s)
      Salie ZL, Kirby KA, Michailidis E, Marchand B, Singh K, Rohan LC, Kodama EN, Mitsuya H, Parniak MA, Sarafianos SG.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 113 Issue: 33 Pages: 9274-9276

    • DOI

      10.1073/pnas.1605223113

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A Novel Peptide Derived from the Fusion Protein Heptad Repeat Inhibits Replication of Subacute Sclerosing Panencephalitis Virus In Vitro and In Vivo.2016

    • Author(s)
      Watanabe M, Hashimoto K, Abe Y, Kodama EN, Nabika R, Oishi S, Ohara S, Sato M,Kawasaki Y, Fujii N, Hosoya M.
    • Journal Title

      PLoS One.

      Volume: 11 Issue: 9 Pages: e0162823-e0162823

    • DOI

      10.1371/journal.pone.0162823

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] エピジェネティック制御を利用する新規医薬資源の開拓2016

    • Author(s)
      浅井禎吾,大島吉輝
    • Journal Title

      生化学 「みにれびゅー」

      Volume: 88 Pages: 643-648

    • NAID

      40020998625

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 微生物の可能性を開拓する-多様な新奇化合物合成のための新しいアプローチ-2016

    • Author(s)
      浅井禎吾,大島吉輝
    • Journal Title

      現代化学 「解説」

      Volume: 9 Pages: 21-26

    • Related Report
      2016 Annual Research Report
  • [Journal Article] A lanthipeptide-like N-terminal leader region guides peptide epimerization by radical SAM epimerases - implications for RiPP evolution.2016

    • Author(s)
      S. W. Fuchs, G. Lackner, B. I. Morinaka, Y. Morishita, T. Asai, S. Riniker, J. Piel
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 55 Issue: 40 Pages: 12330-12333

    • DOI

      10.1002/anie.201602863

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Development of 2-beta Seleno Nucleoside Analogs as Irreversible Inhibitors for Viral Polymerases2018

    • Author(s)
      Yasuaki Kimura, Yushi Niimi, Hideo Katakura, Tetsuro Suzuki, Tsutomu Murakami, EiichiKodama, Hiroshi Abe
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of cell encapsulated gel system for secretion offunctional exosomes in cell therapy.2018

    • Author(s)
      Mami Hirano, Masaya Hagiwara, Nahoko Bailey Kobayashi, Tetsuhiko Yoshida, Eiichi N.Kodama, and Ikuhiko Nakase.
    • Organizer
      The 24th Peptide Forum in Kyoto 2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] 生合成経路の再構築と再設計による糸状菌ジテルペノイドピロンライブラリーの構築と生物活性評価2018

    • Author(s)
      塚田健人,金子秋穂,新木翔之,河治久実,児玉栄一,倉石貴透,村上一馬,入江一浩,平田尚也,諫田泰成,浅井禎吾
    • Organizer
      第36回メディシナルケミストリーシンポジウム 日本薬学会 医薬化学部会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Characterization of novel HIV-1 inhibitorstargeting Gag-TSG101 interaction.2018

    • Author(s)
      Siarot Lowela, Chutiwitoonchai Nopporn, 佐藤洋隆, Chang Hao, 小谷治, 横山勝, 佐藤裕徳, 藤野真之, 村上努, 近藤恭光, 本田香り, 長田裕之, 上田一樹, 伊藤嘉浩, 青野俊裕, 児玉栄一, 黒田和道, 武井正美, 間陽子
    • Organizer
      第32回日本エイズ学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ウイルスポリメラーゼの不可逆阻害を目指した新規2'-b-セレノ核酸アナログの創製2018

    • Author(s)
      村上 努, 木村康明, 新美結士, 藤野真之, 片倉秀雄, 鈴木哲朗, 児玉栄一, 阿部 洋
    • Organizer
      第32回日本エイズ学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] サイトカイニンによるジョロウグモ内生糸状菌の二次代謝活性化2017

    • Author(s)
      森下陽平,岡崎裕亮, 大島吉輝, 浅井禎吾
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] ゲノムマイニングと麹菌異種生産によるジョロウグモ内生糸状菌の新規ポリケタイド類の開拓2017

    • Author(s)
      塚田健人, 伊藤史織, 網谷雄志, 大島吉輝, 浅井禎吾
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 多様性拡大抽出物を利用した構造多様な新規メロテルペノイド型化合物ライブラリーの創出2017

    • Author(s)
      河合航輔,中城陽太,菊地晴久,大島吉輝
    • Organizer
      第7回食品薬学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Humulene の構造を基盤とした構造多様性指向型テルペノイドアルカロイド様化合物ライブラリーの構築2017

    • Author(s)
      西村壮央,菊地晴久,權垠相,川井絢矢,大島吉輝
    • Organizer
      第35回メディシナルケミストリーシンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 植物ホルモンを用いる糸状菌休眠型二次代謝経路の活性化2017

    • Author(s)
      森下陽平, 岡崎裕亮, 羅伊伊, 萩原大祐, 高橋弘喜, 大島吉輝, 浅井禎吾
    • Organizer
      第17回糸状菌分子生物学コンファレンス,
    • Related Report
      2017 Annual Research Report
  • [Presentation] ゲンボイヤ配合錠(GEN;EVG/COBI/FTC/TAF)投与時の耐性発現症例の検討2017

    • Author(s)
      田沼順子,潟永博之,岡慎一,児玉栄一,中本泰充,池田篤史,小倉直樹,Michael E. Abram,Nicolas A. Margot,Stephanie Cox,Christian Callebaut,Moupali Das
    • Organizer
      第31回日本エイズ学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Characteristics of Hospital Damage and Challenges of Disaster Mitigation Related to the 2016Kumamoto Earthquakes in Japan.2017

    • Author(s)
      Hitomi Maeda, Satoko Iyama, Chiharu Matsumoto, Kimiyo Nanke and Eiichi Kodama
    • Organizer
      International Nursing Research Conference 2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] ジョロウグモ内生糸状菌のポストゲノム型天然物探索2016

    • Author(s)
      浅井禎吾,塚田健人,森下陽平,伊藤史織,網谷雄志,岡崎裕亮,児玉栄一,大島吉輝
    • Organizer
      第58回天然物有機化合物討論会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] tructural Basis of Inhibitionand Resistance Mechanism to EFdA,a highly potent NRTI2016

    • Author(s)
      Zhe Li, Karen A. Kirby, Bruno Marchand, Eleftherios Michailidis, Eiichi N.Kodama, Lisa C.Rohan, Hiroaki Mitsuya, Michael A. Parniak, and Stefan G. Sarafianos.
    • Organizer
      Cold Spring Harbor Laboratory Meetings Retroviruses
    • Place of Presentation
      New York City(USA)
    • Year and Date
      2016-05-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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