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Synthesis and evaluation of 2',4'-bridged nucleic acid with a phenoxazine base

Research Project

Project/Area Number 15K08024
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Drug development chemistry
Research InstitutionOsaka University

Principal Investigator

Nakagawa Osamu  大阪大学, 薬学研究科, 招へい教員 (90380691)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords核酸化学 / 核酸医薬 / 人工核酸 / 糖部架橋型核酸
Outline of Final Research Achievements

We designed and synthesized a novel artificial 2’,4’-methylene bridged nucleic acid with a phenoxazine nucleobase (named BNAP). Oligonucleotide containing BNAP showed higher binding affinities toward complementary DNA and RNA. Thus, BNAP is a promising candidate for oligonucleotide therapeutics, especially for those requiring high duplex-forming ability.
On the other hand, we developed a novel artificial nucleic acid containing a 9-azaphenoxazine nucleobase (9-TAP), which behaves as a cytosine (C) analog as well as a thymine (T) analog. Oligonucleotides containing 9-TAP could form stable duplexes via metal-mediated base pairs with C and T, via AgI and HgII, respectively. Duplexes bearing the mismatched base pair 9-TAP-C were effectively stabilized in the presence of CuII. Thus, 9-TAP is expected to have applications in DNA nanotechnology via the formation of various nanostructures triggered by different metal ions.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (14 results)

All 2017 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (13 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Synthesis and thermal stabilities of oligonucleotides containing 2'-O,4'-C-methylene bridged nucleic acid with a phenoxazine base2017

    • Author(s)
      Yuki Kishimoto, Akane Fujii, Osamu Nakagawa, Tetsuya Nagata, Takanori Yokota, Yoshiyuki Hari, Satoshi Obika
    • Journal Title

      Org. Biomol. Chem.

      Volume: 15 Issue: 38 Pages: 8145-8152

    • DOI

      10.1039/c7ob01874f

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] Formation of various metal-mediated base pairs by a 9-azaphenoxazine nucleobase2017

    • Author(s)
      Akane Fujii, Yuki Kishimoto, Osamu Nakagawa, Satoshi Obika
    • Organizer
      44th International Symposium on Nucleic Acids Chemistry (ISNAC2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] フェノキサジン人工塩基核酸類の合成と機能評価2017

    • Author(s)
      中川 治, 岸本悠希, 藤井 茜, 中辻悠輔, 小比賀 聡
    • Organizer
      第47回 複素環化学討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 9-アザフェノキサジン人工塩基核酸の金属錯体形成能2017

    • Author(s)
      藤井 茜, 岸本悠希, 中辻悠輔, 中川 治, 小比賀 聡
    • Organizer
      第67回 日本薬学会 近畿支部総会・大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] N4位に2-(2-アミノエトキシ)フェニル基を有するシチジン誘導体の合成と機能評価2017

    • Author(s)
      中辻悠輔, 藤井 茜, 岸本悠希, 中川 治, 小比賀 聡
    • Organizer
      第67回 日本薬学会 近畿支部総会・大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Synthesis and Properties of Oligonucleotides Containing 9-Azaphenoxazine2017

    • Author(s)
      Akane Fujii, Yuki Kishimoto, Osamu Nakagawa, Satoshi Obika
    • Organizer
      7th Cambridge Symposium on Nucleic Acids Chemistry and Biology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 2',4'-Bridged Nucleic Acid with 9-(Aminoethoxy)phenoxazine: Synthesis and Duplex-Forming Abilities2017

    • Author(s)
      Yuki Kishimoto, Akane Fujii, Osamu Nakagawa, Satoshi Obika
    • Organizer
      7th Cambridge Symposium on Nucleic Acids Chemistry and Biology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 9-アザフェノキサジン人工塩基核酸の合成と三重鎖形成能評価2017

    • Author(s)
      藤井 茜, 岸本悠希, 中川 治, 小比賀 聡
    • Organizer
      日本核酸医薬学会 第3回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 9-(アミノエトキシ)フェノキサジン塩基を有する糖部架橋型人工核酸の二重鎖形成能評価2017

    • Author(s)
      岸本悠希, 藤井 茜, 中川 治, 小比賀 聡
    • Organizer
      日本核酸医薬学会 第3回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Synthesis and evaluation of 2',4'-bridged nucleic acid with 9-(aminoethoxy)phenoxazine2017

    • Author(s)
      Yuki Kishimoto, Akane Fujii, Osamu Nakagawa, Satoshi Obika
    • Organizer
      The 10th Seoul-Kyoto-Osaka Joint Symposium on Pharmaceutical Sciences for Young Scientists
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 塩基部に9-(アミノエトキシ)フェノキサジンを有する糖部架橋型人工核酸BNAP-AEOの合成と評価2017

    • Author(s)
      岸本悠希, 中川 治, 小比賀 聡
    • Organizer
      日本薬学会 第137年会
    • Place of Presentation
      仙台, 宮城
    • Related Report
      2016 Research-status Report
  • [Presentation] フェノキサジン塩基を有する糖部架橋型人工核酸の合成と評価2016

    • Author(s)
      岸本悠希, 中川 治, 小比賀 聡
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-28
    • Related Report
      2015 Research-status Report
  • [Presentation] 9-アザフェノキサジン塩基を有する人工核酸の合成と機能評価2016

    • Author(s)
      藤井 茜, 岸本悠希, 中川 治, 小比賀 聡
    • Organizer
      第66回 日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪薬科大学, 大阪
    • Related Report
      2016 Research-status Report
  • [Presentation] Development of 2',4'-Bridged Nucleic Acid with a Phenoxazine base2016

    • Author(s)
      Yuki Kishimoto, Osamu Nakagawa, Satoshi Obika
    • Organizer
      IS3NA, XXII International Roundtable
    • Place of Presentation
      Paris, France
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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