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Development of novel gene detection method using artificial nucleic acid capable of recognizing damaged bases

Research Project

Project/Area Number 17K19494
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Pharmaceutical Sciences and related fields
Research InstitutionKyushu University

Principal Investigator

Taniguchi Yosuke  九州大学, 薬学研究院, 准教授 (00452714)

Project Period (FY) 2017-06-30 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords酸化損傷塩基 / 人工核酸 / DNA合成酵素 / 増幅反応 / 槽副反応 / オキソグアノシン / 人工核酸トリリン酸体 / 位置特定法
Outline of Final Research Achievements

It has been suggested that the amount of oxidative nucleoside damage in DNA due to stress and reactive oxygen species is related with various diseases. However, there is no general method for sequence specific detection of oxidative damaged nucleobases in DNA. Therefore, we have designed a new artificial nucleoside analogues and succeeded in chemical synthesis. Also, we have succeeded in developing new technology capable of recognizing and detecting the oxidative damaged nucleobases using artificial nucleoside analogues and DNA polymerase. In addition, the results of this study suggesting that the presence of oxidative damaged nucleobases may be involved in transversion mutations that may be involved in carcinogenesis were obtained.

Academic Significance and Societal Importance of the Research Achievements

本研究により得られた成果は、ストレスなどにより引き起こされる遺伝子の傷と考えられるDNA酸化損傷と疾患との関連性を明らかにする事を可能にする技術への展開が期待される。すなわち、実施した研究内容により新規核酸分子の化学合成や新機能の解明といった学術的に意義深いものだけで無く、本技術の展開による様々な疾患の早期診断技術の開発も可能で社会的にも非常に意義深い研究成果が得られた。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (29 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (20 results) (of which Int'l Joint Research: 6 results,  Invited: 2 results) Remarks (3 results)

  • [Int'l Joint Research] Department of Pharmacy/Faculty of Medicine/University of Malaya(マレーシア)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Department of Pharmacy/Faculty of Pharmacy/Mahidol University(タイ)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Oxidative-stress-driven in vivo mutagenesis induced by oral administration of potassium bromate in the small intestines of gpt delta mice2020

    • Author(s)
      Aoki Y, Taniguchi Y, Matsumoto M, Matsumoto M, Ohno M, Masumura K, Sasaki S, Tsuzuki T, Yamamoto M, Nohmi T
    • Journal Title

      Mutation Research

      Volume: 850-851 Pages: 503136-503136

    • DOI

      10.1016/j.mrgentox.2020.503136

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of the 2-Substituted Adenosine-1,3-diazaphenoxazine 5′-Triphosphate Derivatives on the Single Nucleotide Primer Extension Reaction by DNA Polymerase2019

    • Author(s)
      Taniguchi Y., Sagara I., Nagata Y., Kikukawa Y., Sasaki S
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 67 Issue: 10 Pages: 1123-1130

    • DOI

      10.1248/cpb.c19-00453

    • NAID

      130007722037

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2019-10-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of γ-N-modified 8-oxo-2’-deoxyguanosine triphosphate and its characterization2019

    • Author(s)
      Ninticha Thavoncharoensuba, Kento Maruyama, Choon Han Heh, Kok Hoong Leong, Hui Shi, Yoshiharu Shigematsu, Shigeki Sasaki, and Yosuke Taniguchi
    • Journal Title

      NUCLEOSIDES, NUCLEOTIDES AND NUCLEIC ACIDS

      Volume: 印刷中 Issue: 8 Pages: 578-589

    • DOI

      10.1080/15257770.2019.1586919

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development of Damaged Nucleoside Mimics for Inhibition of Their Repair Enzymes2017

    • Author(s)
      Taniguchi Y
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 137 Issue: 3 Pages: 293-300

    • DOI

      10.1248/yakushi.16-00231-2

    • NAID

      130005396861

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2017-03-01
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] DNA配列中での8-オキソグアノシン発生位置検出を目指したデアザプリン人工ヌクレオチデオチドの開発と評価2020

    • Author(s)
      長田 悠佑、谷口 陽祐、相良 委公子、菊川 誉也、佐々木茂貴
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 8-オキソグアノシンを選択的に認識するデアザプリン人工ヌクレオチドの開発2019

    • Author(s)
      長田悠佑、谷口陽祐、相良委公子、菊川誉也、佐々木茂貴
    • Organizer
      第56回化学関連支部合同九州大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 8-オキソグアノシンを選択的に認識するデアザプリン人工ヌクレオチドの開発2019

    • Author(s)
      長田悠佑、谷口陽祐、相良委公子、菊川誉也、佐々木茂貴
    • Organizer
      第31回若手研究者のためのセミナー
    • Related Report
      2019 Annual Research Report
  • [Presentation] 損傷DNAを配列特異的に増やす、探る人工核酸2019

    • Author(s)
      谷口陽祐
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 酸化損傷塩基を認識可能なフェノキサジン環を有する人工ヌクレオチドの合成と機能評価2019

    • Author(s)
      谷口陽祐、菊川誉也、相良委公子、長田悠佑、佐々木茂貴
    • Organizer
      第45回反応と合成の進歩シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] Synthesis and evaluation of deazapurine nucleotide analogue selectivity recognizing 8-oxo-2'-deoxyguanosine in DNA2019

    • Author(s)
      Yusuke Nagata, Yosuke Taniguchi, Ikuko Sagara, Yoshiya KIkukawa, Shigeki Sasaki
    • Organizer
      第46回国際核酸化学シンポジウム(ISNAC2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of 7,8-disubstituted 7-deazadG nucleotide derivatives as 8-oxo-dG triphosphatase inhibitors2019

    • Author(s)
      Hui Shi, Yizhen Yin, Shigeki Sasaki, Yosuke Taniguchi
    • Organizer
      第46回国際核酸化学シンポジウム(ISNAC2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 8-オキソグアノシン選択的認識を目指したデアザプリン人工ヌクレオチドの開発と評価2019

    • Author(s)
      長田 悠佑、谷口 陽祐、相良 委公子、菊川 誉也、佐々木茂貴
    • Organizer
      第36回日本薬学会九州支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] γ-アミドトリリン酸の簡易的な合成法の確立と酵素伸長反応への利用2019

    • Author(s)
      桜田 喬登、谷口 陽祐、長田 悠佑、佐々木 茂貴
    • Organizer
      第36回日本薬学会九州支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] トリリン酸γ位修飾体による酸化損傷修復酵素への結合と活性阻害評価2018

    • Author(s)
      丸山健登、重松慶治、石卉、佐々木茂貴、谷口陽祐
    • Organizer
      第55回化学関連支部合同九州大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Synthesis and evaluation of modified 7-deaza-dG triphosphate derivatives for 8-oxo-dGTP mimicry2018

    • Author(s)
      Yosuke Taniguchi, Hui Shi, Yoshiharo Shigematsu, Shigeki Sasaki
    • Organizer
      XXIII International Roundtable on Nucleosides, Nucleotides and Nucleic Acids
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] γ位修飾トリリン酸によるhMTH1への結合と活性阻害評価2018

    • Author(s)
      丸山健登、重松慶治、石卉、佐々木茂貴、谷口陽祐
    • Organizer
      第30回若手研究者のためのセミナー
    • Related Report
      2018 Research-status Report
  • [Presentation] 7,8位修飾デアザプリン核酸誘導体の合成と酵素阻害能の評価2018

    • Author(s)
      第48回複素環討論会
    • Organizer
      石卉、尹胎貞、佐々木茂貴、谷口陽祐
    • Related Report
      2018 Research-status Report
  • [Presentation] Synthesisand evaluation of 7,8-disubstituted 7-deazad-dGTP derivatives as hMTH1 Inhibitors2018

    • Author(s)
      Hui Shi, Zhen Yi Yin, Shigeki Sasaki, Yosuke Taniguchi
    • Organizer
      第45回国際核酸化学シンポジウム
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 酸化損傷核酸のγ位修飾体による修復酵素への結合と活性阻害評価2018

    • Author(s)
      丸山 健登、Ninticha THAVONCHAROENSUB、重松 慶治、佐々木 茂貴、谷口 陽祐
    • Organizer
      日本薬学会第139回年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 7,8修飾7-デアザグアノシントリリン酸誘導体によるhMTH1阻害剤の開発2018

    • Author(s)
      石 卉、尹 貽貞、佐々木 茂貴、谷口 陽祐
    • Organizer
      日本薬学会第139回年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Synthesis and evaluation of substituted 7-deazadGtriphosphate derivatives as hMTH1 inhibitors2018

    • Author(s)
      Yosuke Taniguchi
    • Organizer
      KU-NTU Joint International Symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 8-Oxo-dG認識の向上を目指した2-Chloro-Adapの合成と評価2017

    • Author(s)
      相良委公子、谷口陽祐、菊川誉也、佐々木茂貴
    • Organizer
      第54回化学関連支部合同九州大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 8位修飾7デアザグアノシン誘導体による核酸修復酵素阻害剤の創製2017

    • Author(s)
      谷口陽祐、尹貽貞、石卉、重松慶治、佐々木茂貴
    • 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 Research-status Report
  • [Presentation] Synthesis and evaluation of nucleoside analoguesfor the recognition of a TA base pair within the triplex DNA2017

    • Author(s)
      Hui Shi, Shigeki Sasaki, Yosuke Taniguchi
    • Organizer
      The 1st Annual Meeting of Japan Society of Nucleic Acids Chemistry
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Remarks] http://bioorg.phar.kyushu-u.ac.jp/index.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] http://bioorg.phar.kyushu-u.ac.jp/index.html

    • Related Report
      2018 Research-status Report
  • [Remarks] 九州大学薬学研究院 生物有機合成化学分野

    • URL

      http://bioorg.phar.kyushu-u.ac.jp/index.html

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-07-21   Modified: 2021-02-19  

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