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Study on artificial nucleic acids design based on the glycosidic bond angle control

Research Project

Project/Area Number 24790110
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Drug development chemistry
Research InstitutionNagoya University

Principal Investigator

KODAMA Tetsuya  名古屋大学, 創薬科学研究科, 准教授 (00432443)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords核酸 / 有機化学 / 核酸医薬 / 薬学 / 創薬科学 / 人工核酸
Research Abstract

Several artificial nucleic acids bearing 7-deazapurine-analog were synthesized and those torsion angles about glycosidic bond were estimated. We found that bridged nucleic acids have a similar glycosidic bond angle to RNA to stabilize the double stranded oligonucleotides. Moreover, nucleic acids bearing tetrahydropyran or cyclohehene as a sugar moiety were synthesized. These artificial nucleic acids showed a high resistance to 5'-3' exonuclease, and one of nucleic acids bearing a tetrahydropyran sugar present a high stabilization property of duplex oligonucleotides.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (26 results)

All 2014 2013 2012 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (21 results) (of which Invited: 1 results)

  • [Journal Article] Photoinduced Changes in Hydrogen Bonding Patterns of 8-Thiopurine Nucleobase Analogues in a DNA Strand.2014

    • Author(s)
      K. Morihiro, T. Kodama, S. Mori, S. Obika
    • Journal Title

      Org. Biomol. Chem.

      Volume: 12 Issue: 15 Pages: 2468-2473

    • DOI

      10.1039/c3ob42427h

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Light-triggered Strand Exchange Reaction Using the Change in the Hydrogen Bonding Pattern of the Nucleobase Analog2014

    • Author(s)
      K. Morihiro, T. Kodama, R. Waki, S. Obika
    • Journal Title

      Chem. Sci.

      Volume: 5 Issue: 2 Pages: 744-750

    • DOI

      10.1039/c3sc51987b

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Selenomethylene Locked Nucleic Acid Enables Reversible Hybridization in Response to Redox Changes2013

    • Author(s)
      Kunihiko Morihiro
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 52 Issue: 19 Pages: 5074-5078

    • DOI

      10.1002/anie.201300555

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of Selenomethylene-locked Nucleic Acid (SeLNA)-modified Oligonucleotides by Polymerases2012

    • Author(s)
      Megan Wheeler
    • Journal Title

      Chemical Communications

      Volume: 48 Issue: 89 Pages: 11020-11022

    • DOI

      10.1039/c2cc36464f

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Amido-Bridged Nucleic Acids (AmNAs): Synthesis, Duplex Stability, Nuclease Resistance, and in Vitro Antisense Potency2012

    • Author(s)
      Aiko Yahara, Ajaya Ram Shrestha, Tsuyoshi Yamamoto, Yoshiyuki Hari, Takashi Osawa, Masaki Yamaguchi, Masaru Nishida, Tetsuya Kodama, Satoshi Obika
    • Journal Title

      ChemBioChem

      Volume: vol.13 Issue: 17 Pages: 2513-2516

    • DOI

      10.1002/cbic.201200506

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] ヌクレオシド・ヌクレオチドならびにオリゴヌクレオチドのメディシナルケミストリー2014

    • Author(s)
      兒玉哲也
    • Organizer
      中部地区医療・バイオ系シーズ発表会
    • Place of Presentation
      ウインクあいち(愛知)
    • Year and Date
      2014-12-12
    • Related Report
      2013 Final Research Report
  • [Presentation] 架橋型人工核酸(BNA)の核酸医薬への応用2014

    • Author(s)
      兒玉哲也
    • Organizer
      名古屋大学予防早期医療創成センター第4回ワークショップ
    • Place of Presentation
      名古屋大学(愛知)
    • Year and Date
      2014-01-29
    • Related Report
      2013 Final Research Report
  • [Presentation] 舟形ピラノース核酸類の合成とその標的結合能2013

    • Author(s)
      森和土、兒玉哲也、小比賀聡
    • Organizer
      第39回反応と合成の進歩シンポジウム
    • Place of Presentation
      九州大学(福岡)
    • Year and Date
      2013-11-06
    • Related Report
      2013 Final Research Report
  • [Presentation] Syntheses and properties of nucleic acids having constrained pyranose as the sugar moiety2013

    • Author(s)
      Kazuto Mori, Tetsuya Kodama, Satoshi Obika
    • Organizer
      The 40^<th> international symposium on nucleic acids chemistry
    • Place of Presentation
      神奈川大学(神奈川)
    • Related Report
      2013 Final Research Report
  • [Presentation] Selenomethylene locked nucleic acid (SeLNA) bearing a purine base2013

    • Author(s)
      Yoshihiro Moai, Tetsuya Kodama, Kunihiko Morihiro, Hidekazu Hiroaki, Satoshi Obika
    • Organizer
      The 40^<th> international symposium on nucleic acids chemistry
    • Place of Presentation
      神奈川大学(神奈川)
    • Related Report
      2013 Final Research Report
  • [Presentation] 架橋型シクロヘキセニル核酸の合成と評価2013

    • Author(s)
      百相義大、廣明秀一、小比賀聡、兒玉哲也
    • Organizer
      第23回アンチセンスシンポジウム
    • Place of Presentation
      徳島大学(徳島)
    • Related Report
      2013 Final Research Report
  • [Presentation] Syntheses and properties of nucleic acids having constrained pyranose as the sugar moiety2013

    • Author(s)
      Kazuto Mori, Tetsuya Kodama, Satoshi Obika
    • Organizer
      The 40th International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      神奈川
    • Related Report
      2013 Annual Research Report
  • [Presentation] Selenomethylene Locked Nucleic Acid (SeLNA) Bearing a Purine Base2013

    • Author(s)
      Yoshihiro Moai, Tetsuya Kodama, Kunihiko Morihiro, Hidekazu Hiroaki, Satoshi Obika
    • Organizer
      The 40th International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      神奈川
    • Related Report
      2013 Annual Research Report
  • [Presentation] 架橋型シクロヘキセニル核酸の合成と評価2013

    • Author(s)
      百相義大、廣明秀一、小比賀聡、兒玉哲也
    • Organizer
      第23回アンチセンスシンポジウム
    • Place of Presentation
      徳島
    • Related Report
      2013 Annual Research Report
  • [Presentation] 2',4'-BNA/LNA-プリン塩基類縁体の二重鎖形成能に及ぼす二面角χの影響2013

    • Author(s)
      原孝志, 兒玉哲也, 竹垣裕美, 森廣邦彦, 伊藤浩介, 小比賀聡
    • Organizer
      日本薬学会 第133年会
    • Place of Presentation
      神奈川県横浜市
    • Related Report
      2012 Research-status Report
  • [Presentation] セレノメチレン架橋型人工核酸の開発と酸化還元スイッチへの応用2013

    • Author(s)
      森廣邦彦, 兒玉哲也, 肯特夫, 百相義大, Veedu Rakesh.N, 小比賀聡
    • Organizer
      日本薬学会 第133年会
    • Place of Presentation
      神奈川県横浜市
    • Related Report
      2012 Research-status Report
  • [Presentation] 核酸化学: 核酸医薬創出に向けた 新たなコンホメーション固定型人工核酸の開発2013

    • Author(s)
      兒玉哲也
    • Organizer
      第2回岐阜構造生物学・医学・論理的創薬研究会シンポジウム
    • Place of Presentation
      岐阜県岐阜市
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Synthesis and properties of a nucleic acid bearing boat-shaped pyranose sugar2012

    • Author(s)
      Kazuto Mori, Tetsuya Kodama, Satoshi Obika
    • Organizer
      13th Tetrahedron Symposium - Asia Edition
    • Place of Presentation
      台湾、台北市
    • Related Report
      2012 Research-status Report
  • [Presentation] Torsion angle around glycosidic bond on BNA/LNA-purine strongly affects duplex stability2012

    • Author(s)
      Tetsuya Kodama, Takashi Hara, Yumi Takegaki, Kunihiko Morihiro, Kosuke Ramon Ito, Obika Satoshi
    • Organizer
      The 39th International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      愛知県名古屋市
    • Related Report
      2012 Research-status Report
  • [Presentation] チミン塩基をもつセレノメチレン架橋型人工核酸の合成と基本的性質2012

    • Author(s)
      兒玉哲也, 森廣邦彦, 肯特夫, 百相義大, Veedu Rakesh.N, 小比賀聡
    • Organizer
      アンチセンス・遺伝子・デリバリーシンポジウム 2012
    • Place of Presentation
      宮城県仙台市
    • Related Report
      2012 Research-status Report
  • [Presentation] Investigation of the factor affecting the duplex-forming ability of boat-shaped glucopyranosyl nucleic acid2012

    • Author(s)
      Kazuto Mori, Tetsuya Kodama, Satoshi Obika
    • Organizer
      XX International Round Table on Nucleosides, Nucleotides and Nucleic Acids
    • Place of Presentation
      カナダ、モントリオール市
    • Related Report
      2012 Research-status Report
  • [Presentation] Synthesis and hybridization property of oligonucleotides containing 2’,4’-BNA-7-deazaguanine analog.2012

    • Author(s)
      Takashi Hara, Yumi Takegaki, Kunihiko Morihiro, Kosuke Ramon Ito, Tetsuya Kodama, Satoshi Obika
    • Organizer
      XX International Round Table on Nucleosides, Nucleotides and Nucleic Acids
    • Place of Presentation
      カナダ、モントリオール市
    • Related Report
      2012 Research-status Report
  • [Presentation] 糖部構造を固定化したグルコピラノシル核酸の合成と構造に関する研究2012

    • Author(s)
      兒玉哲也, 森和土, 小比賀聡
    • Organizer
      第58回 日本薬学会東海支部大会
    • Place of Presentation
      静岡県静岡市
    • Related Report
      2012 Research-status Report
  • [Presentation] 架橋型人工核酸(BNA)の核酸医薬への応用

    • Author(s)
      兒玉哲也
    • Organizer
      名古屋大学 予防早期医療創成センター 第4回ワークショップ
    • Place of Presentation
      愛知
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヌクレオシド・ヌクレオチドならびにオリゴヌクレオチドのメディシナルケミストリー

    • Author(s)
      兒玉哲也
    • Organizer
      中部地区 医療・バイオ系シーズ発表会
    • Place of Presentation
      愛知
    • Related Report
      2013 Annual Research Report
  • [Presentation] 舟型ピラノース核酸類の 合成とその標的結合能

    • Author(s)
      森和土、兒玉哲也、小比賀聡
    • Organizer
      第39回反応と合成の進歩シンポジウム
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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