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Identification of new target molecule using natural products: Toward development of anti tuberculosis molecules

Research Project

Project/Area Number 20H02869
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
Research InstitutionOsaka Metropolitan University (2022-2023)
Osaka City University (2020-2021)

Principal Investigator

Tetsuro Shinada  大阪公立大学, 大学院理学研究科, 教授 (30271513)

Co-Investigator(Kenkyū-buntansha) 保野 陽子  九州大学, 理学研究院, 助教 (40736500)
荒井 雅吉  大阪大学, 大学院薬学研究科, 教授 (80311231)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2023: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2022: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2021: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywordsペプチド / 天然物 / 結核 / 標的分子 / 抗菌活性 / 抗結核分子 / 分子標的 / 結核菌
Outline of Research at the Start

結核の脅威が再認識されている現代において、有効な薬剤開発は急務の課題である。「結核菌に対抗するための糸口をどう探るのか?」それが本研究の核心をなす問いである。その手掛かりを、分子標的が明らかでないペプチド系天然物に求め、その分子標的を解明することで、新しくかつ有効な抗結核薬の開発を進める。

Outline of Final Research Achievements

Tuberculosis (TB) is one of the contagious and infectious diseases caused by Mycobacterium tuberculosis (Mtb). TB drug discovery and development recognize an important subject in the world. In this study, we focused on antrimycins which display anti-Mtb activities. Although these natural products were found ca. 50 years ago, the mode of action and target molecules have been unknown. These facts prompt us to study the target molecule(s) of antrimycins by total syntheses, biological activity tests, and screening of the target molecules using the synthetic antrimycins. As a result, we found several candidate molecules which would associate with the mode of action of antriymcins. These results would contribute to the development of efficient anti-Mtb drugs based on the antrimycins and its target molecule.

Academic Significance and Societal Importance of the Research Achievements

世界保健機構(WHO)が警鐘を鳴らし続けているように、結核を制御・抑制する薬剤開発は世界的に重要な課題である。その解決法の提供は、貧困をなくす、健康社会をつくるといったSDGs項目に合致する。本研究で得られた成果は、結核に対抗する新しい薬剤開発にむけた分子基盤を提供するものであり、健康社会の実現に貢献する社会的意義を備えている。現在、天然物の標的分子の絞り込みが進んでいる。研究をさらに進めるによって新しい抗結核薬創出に向けた一歩を踏み出すことができるようになると期待される。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (21 results)

All 2024 2023 2022 2021 2020 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 3 results) Presentation (9 results) (of which Int'l Joint Research: 1 results) Remarks (2 results)

  • [Journal Article] First Total Syntheses of Beauvericin A and <i>allo</i>-Beauvericin A2024

    • Author(s)
      Kozakai Natsumi、Endo Seiya、Nakayama Atsushi、Horinouchi Riku、Yoshida Makoto、Arai Masayoshi、Shinada Tetsuro
    • Journal Title

      ACS Omega

      Volume: 9 Issue: 10 Pages: 12228-12236

    • DOI

      10.1021/acsomega.4c00278

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of the cirratiomycin biosynthesis gene cluster in Streptomyces cirratus: elucidation of the biosynthetic pathways for 2,3‐diaminobutyric acid and hydroxymethylserine2024

    • Author(s)
      Sakata Shunki、Li Jiafeng、Yasuno Yoko、Shinada Tetsuro、Shin‐ya Kazuo、Katsuyama Yohei、Ohnishi Yasuo
    • Journal Title

      Chemistry - A European Journal

      Volume: - Issue: 28

    • DOI

      10.1002/chem.202400271

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanisms of Sugar Aminotransferase-like Enzymes to Synthesize Stereoisomers of Non-proteinogenic Amino Acids in Natural Product Biosynthesis2023

    • Author(s)
      Kurosawa Sumire、Okamura Hironori、Yoshida Ayako、Tomita Takeo、Sone Yusuke、Hasebe Fumihito、Shinada Tetsuro、Takikawa Hirosato、Kosono Saori、Nishiyama Makoto
    • Journal Title

      ACS Chemical Biology

      Volume: 18 Issue: 2 Pages: 385-395

    • DOI

      10.1021/acschembio.2c00823

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Formylation Reaction of Amines Using <i>N</i>-Formylcarbazole2022

    • Author(s)
      Kang Bubwoong、Shimizu Yuki、Tamura Yusaku、Fukuda Eigo、Hamamoto Ken-ichiro、Uchida Yuichiro、Yasuno Yoko、Nakayama Atsushi、Satoh Tetsuya、Kuse Masaki、Shinada Tetsuro
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 70 Issue: 7 Pages: 492-497

    • DOI

      10.1248/cpb.c22-00161

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2022-07-01
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stereoselective Synthesis of Dehydroamino Acids and Its Application to the Synthesis of Nitrogen-containing Natural Products2022

    • Author(s)
      Yasuno Yoko、Okamura Hironori、Shinada Tetsuro
    • Journal Title

      Journal of Synthetic Organic Chemistry, Japan

      Volume: 80 Issue: 4 Pages: 331-342

    • DOI

      10.5059/yukigoseikyokaishi.80.331

    • ISSN
      0037-9980, 1883-6526
    • Year and Date
      2022-04-01
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stereoselective Synthesis of (2S,3R)- and (2S,3S)- 2-Amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic Acid2021

    • Author(s)
      Yasuno Yoko、Yamaguchi Shunsuke、Karita Yuma、Sakai Kenta、Okamura Hironori、Nakayama Atsushi、Shinada Tetsuro
    • Journal Title

      HETEROCYCLES

      Volume: 103 Issue: 2 Pages: 965-965

    • DOI

      10.3987/com-20-s(k)70

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective oxidation of alcohol-d1 to aldehyde-d1 using MnO22021

    • Author(s)
      Okamura Hironori、Yasuno Yoko、Nakayama Atsushi、Kumadaki Katsushi、Kitsuwa Kohei、Ozawa Keita、Tamura Yusaku、Yamamoto Yuki、Shinada Tetsuro
    • Journal Title

      RSC Advances

      Volume: 11 Issue: 46 Pages: 28530-28534

    • DOI

      10.1039/d1ra05405h

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stereoselective Synthesis of (2S,6R)‐Diamino‐(5R,7)‐dihydroxy‐heptanoic Acid (DADH): An Unusual Amino Acid from Streptomyces sp. SANK 604042021

    • Author(s)
      Okamura Hironori、Yasuno Yoko、Nakayama Atsushi、Takikawa Hirosato、Shinada Tetsuro
    • Journal Title

      European Journal of Organic Chemistry

      Volume: 2021 Issue: 9 Pages: 1396-1401

    • DOI

      10.1002/ejoc.202001646

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-Acylcarbazole as a Selective Transamidation Reagent2020

    • Author(s)
      B. Kang, Y. Yasuno, H. Okamura, A. Sakai, T. Satoh, M. Kuse, T. Shinada
    • Journal Title

      Bull. Chem. Soc. Jpn.

      Volume: 93 Issue: 8 Pages: 993-999

    • DOI

      10.1246/bcsj.20200116

    • NAID

      130007888018

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of Optically Active (R)- and (S)-β-Arginine from Pyroglutamic Acid2020

    • Author(s)
      Shinada Tetsuro、Yasuno Yoko、Sawai Akira、Sekihara Ai
    • Journal Title

      HETEROCYCLES

      Volume: 101 Issue: 1 Pages: 165-176

    • DOI

      10.3987/com-19-s(f)6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] アントリマイシン類の全合成2023

    • Author(s)
      藤原維吹, 田村優作, 中山淳, 品田哲郎
    • Organizer
      14.43回有機合成若手セミナー「明日の有機合成を担う人のために」
    • Related Report
      2023 Annual Research Report
  • [Presentation] Total Synthesis and Structure Determination of Bipenicilisorin2023

    • Author(s)
      Eigo Fukuda, Ibuki Fujiwara, Kenichiro Hamamoto, Keita Ozawa, Shoki Maruno, Kaiki Motomura, Atsushi Nakayama, Tetsuro Shinada
    • Organizer
      2.The 15th International Kyoto Conference on New Aspects of Organic Chemistry (IKCOC-15)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アントリマイシン類の全合成2023

    • Author(s)
      田村優作,藤原維吹,中山淳,品田哲郎
    • Organizer
      日本化学会第103春季年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] アントリマイシンAvの全合成2022

    • Author(s)
      田村優作、中山淳、品田哲郎
    • Organizer
      日本化学会 第102回春季年会(2022)
    • Related Report
      2021 Annual Research Report
  • [Presentation] 非天然型アミノ酸DADHの全異性体の合成研究2022

    • Author(s)
      岡村 仁則、保野 陽子、中山淳、品田哲郎、滝川浩郷
    • Organizer
      日本農芸化学会 2022年度大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] N-アシルカルバゾールを用いた選択的アミド化反応の開発2021

    • Author(s)
      姜法雄、保野陽子、岡村仁則、酒井明日実、佐藤哲也、久世雅樹、品田哲郎
    • Organizer
      第50回複素環化学討論会
    • Related Report
      2021 Annual Research Report
  • [Presentation] (2S,6R)-ジアミノ-(5R,7)-ジヒドロキシヘプタン酸(DADH)及びその誘導体の立体選択的合成2021

    • Author(s)
      岡村 仁則、保野 陽子、滝川 浩郷、品田 哲郎
    • Organizer
      日本農芸化学会 2021年度大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] N-アシルカルバゾールを用いた選択的アミド化反応の開発2020

    • Author(s)
      姜法雄 、保野陽子 、岡村仁則 、酒井明日実 、佐藤哲也 、久世雅樹 、品田哲郎
    • Organizer
      第62回天然有機化合物討論会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 含アジリジン天然物の推定生合成中間体の合成研究2020

    • Author(s)
      岡村仁則、滝川浩郷、品田哲郎
    • Organizer
      第64回香料・テルペンおよび精油化学に関する討論会( TEAC )
    • Related Report
      2020 Annual Research Report
  • [Remarks] 大阪公立大学大学院理学研究科物質分子系専攻分子変換学研究室

    • URL

      http://www.sci.osaka-cu.ac.jp/chem/henkan/index.html

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
  • [Remarks] 大阪市立大学大学院理学研究科物質分子系専攻分子変換学研究室

    • URL

      http://www.sci.osaka-cu.ac.jp/chem/henkan/index.html

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report

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Published: 2020-04-28   Modified: 2025-01-30  

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