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Creation of new function of chemically-modified cyclized nucleic acids

Research Project

Project/Area Number 16K08153
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Chemical pharmacy
Research InstitutionTohoku University

Principal Investigator

Onizuka Kazumitsu  東北大学, 多元物質科学研究所, 准教授 (00707961)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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)
Keywords機能性核酸 / DNA / RNA / ロタキサン / 切断 / 環状 / 核酸 / 擬ロタキサン / 蛍光ON型プローブ / RNA切断 / 環状核酸 / 翻訳 / クリック反応 / miRNA
Outline of Final Research Achievements

Rotaxane is a molecular architecture consisting of a dumbbell-shaped molecule which is threaded through a molecular ring. To further expand the unique properties of the rotaxane into the chemical biology field, a spontaneous rotaxane formation method with the target would be ideal. For example, a functional nucleic acid, which can spontaneously form the rotaxane-like structure with mRNA, might tightly bind to mRNA and strongly inhibit the translation reaction using the static property of the rotaxane. In this study, we inhibited the translation reaction using a pair of pseudorotaxane-forming oligo DNAs developed by our group. In addition, we found that chemically-modified oligo DNA cleaved the target RNA.

Academic Significance and Societal Importance of the Research Achievements

RNAに対しオリゴヌクレオチド(ON)を用いて二本鎖を形成させ蛋白質発現を制御するアンチセンス法は、長年創薬に向けた研究が行われている。本研究では従来のアプローチとはまったく異なる、標的RNAと強く結合する新しいアプローチを考案した。今回、我々は二つの分子が、「直接共有結合でつながってはいないが外れもしない」というロタキサンの性質に着目した。ロタキサンは、輪の中にひも状の分子が貫通した構造である。標的RNAを軸に、ロタキサン様構造を形成させることで、RNAに巻き付く極めて安定な複合体を形成し、効率的にリボソームの進行を止めることができると考え本研究を実施した。

Report

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

    (26 results)

All 2019 2018 2017 2016 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (17 results) (of which Int'l Joint Research: 6 results,  Invited: 4 results) Remarks (2 results)

  • [Journal Article] Alkyne-Alkyne Photo-cross-linking on the Flipping-out Field2019

    • Author(s)
      Onizuka Kazumitsu、Ishida Kei、Mano Eriko、Nagatsugi Fumi
    • Journal Title

      Organic Letters

      Volume: 21 Issue: 8 Pages: 2833-2837

    • DOI

      10.1021/acs.orglett.9b00817

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vinyldiaminotriazine-acridine conjugate as G-quadruplex alkylating agent2018

    • Author(s)
      Hazemi Madoka E.、Onizuka Kazumitsu、Kobayashi Tomohito、Usami Akira、Sato Norihiro、Nagatsugi Fumi
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 26 Issue: 12 Pages: 3551-3558

    • DOI

      10.1016/j.bmc.2018.05.030

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural optimization of pseudorotaxane-forming oligonucleotides for efficient and stable complex formation2018

    • Author(s)
      Onizuka Kazumitsu、Miyashita Takuya、Chikuni Tomoko、Ozawa Mamiko、Abe Hiroshi、Nagatsugi Fumi
    • Journal Title

      Nucleic Acids Research

      Volume: 46 Issue: 17 Pages: 8710-8719

    • DOI

      10.1093/nar/gky744

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Selective alkylation of T-T mismatched DNA using vinyldiaminotriazine-acridine conjugate2018

    • Author(s)
      Onizuka Kazumitsu、Usami Akira、Yamaoki Yudai、Kobayashi Tomohito、Hazemi Madoka E、Chikuni Tomoko、Sato Norihiro、Sasaki Kaname、Katahira Masato、Nagatsugi Fumi
    • Journal Title

      Nucleic Acids Res.

      Volume: 46 Issue: 3 Pages: 1059-1068

    • DOI

      10.1093/nar/gkx1278

    • NAID

      120006466620

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alkylating probes for the G-quadruplex structure and evaluation of the properties of the alkylated G-quadruplex DNA2018

    • Author(s)
      Sato Norihiro、Takahashi Shuntaro、Tateishi-Karimata Hisae、Hazemi Madoka E.、Chikuni Tomoko、Onizuka Kazumitsu、Sugimoto Naoki、Nagatsugi Fumi
    • Journal Title

      Org. Biomol. Chem.

      Volume: 16 Issue: 9 Pages: 1436-1441

    • DOI

      10.1039/c7ob03179c

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pseudorotaxane formation via the slippage process with chemically-cyclized oligonucleotides2017

    • Author(s)
      Kazumitsu Onizuka, Tomoko Chikuni, Takuya Amemiya, Takuya Miyashita, Kyoko Onizuka, Hiroshi Abe, Fumi Nagatsugi
    • Journal Title

      Nucleic Acids Res.

      Volume: 印刷中 Issue: 9 Pages: 5036-5047

    • DOI

      10.1093/nar/gkx265

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Synthesis of native-like crosslinked duplex RNA and study of its properties2017

    • Author(s)
      Kazumitsu Onizuka, Madoka E. Hazemi, Justin M. Thomas, Leanna R. Monteleone, Ken Yamada, Shuhei Imoto, Peter Beal, Fumi Nagatsugi
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 25 Issue: 7 Pages: 2191-2199

    • DOI

      10.1016/j.bmc.2017.02.034

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 標的核酸を捕らえる新しい反応性分子開発2019

    • Author(s)
      鬼塚和光、永次史
    • Organizer
      日本薬学会 第139年会 薬学における生命指向型化学
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Nucleic Acid Templated Reactions and Automatic Pseudorotaxane Formation2018

    • Author(s)
      Kazumitsu Onizuka, Jumpei Matsuyama, Takuya Miyashita, Yuuya Kawasaki, Kazunobu Igawa, Katsuhiko Tomooka, Fumi Nagatsugi
    • Organizer
      The 1st International Symposium on Middle Molecular Strategy for Young Scientists
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Chemical reactions accelerated on nucleic acids and their applications2018

    • Author(s)
      鬼塚和光、松山潤柄、宮下卓也、Madoka E. Hazemi、永次 史
    • Organizer
      平成30年度化学系学協会東北大会有機化学コロキウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 標的核酸に作用する機能性分子の開発研究2018

    • Author(s)
      鬼塚和光
    • Organizer
      細胞でつながる研究会-Bio. Phys. Chem. 三重点の探索-
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Spontaneous pseudorotaxane formation targeting nucleic acids2018

    • Author(s)
      Kazumitsu Onizuka, Jumpei Matsuyama, Takuya Miyashita, Yuuya Kawasaki, Kazunobu Igawa, Katsuhiko Tomooka, Fumi Nagatsugi
    • Organizer
      XXIII International roundtable on nucleosides, nucleotides and nucleic acids
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Spontaneous pseudorotaxane formation targeting nucleic acids and fluorogenic click chemistry2018

    • Author(s)
      Kazumitsu Onizuka, Jumpei Matsuyama, Takuya Miyashita, Yuuya Kawasaki, Kazunobu Igawa, Katsuhiko Tomooka, Fumi Nagatsugi
    • Organizer
      The 45th International Symposium on Nucleic Acids Chemistry 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 擬ロタキサン形成核酸の開発とその応用研究2018

    • Author(s)
      鬼塚和光、松山潤炳、田口晃史、河崎悠也、井川和宣、友岡克彦、永次 史
    • Organizer
      日本核酸医薬学会第4回年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] RNAの非共有結合性蛍光ラベル化を可能にする蛍光OFF/ON型擬ロタキサン形成核酸の開発2018

    • Author(s)
      松山 潤炳、鬼塚 和光、宮下 卓也、河崎 悠也、井川 和宣、友岡 克彦、永次 史
    • Organizer
      日本化学会 第98春季年会
    • Related Report
      2017 Research-status Report
  • [Presentation] RNA切断能を持つ機能性核酸の開発2018

    • Author(s)
      鬼塚 和光、田口 晃史、永次 史
    • Organizer
      日本化学会 第98春季年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 標的RNAを化学的に切断する機能性核酸の開発2018

    • Author(s)
      鬼塚 和光、田口 晃史、永次 史
    • Organizer
      日本薬学会138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 環状化核酸を用いたスリッピングによる擬ロタキサン構造形成のメカニズム研究2017

    • Author(s)
      鬼塚 和光, 千国 友子, 宮下 卓也, 永次 史
    • Organizer
      日本薬学会 第137年会
    • Place of Presentation
      東北大学(宮城県仙台市)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] Mechanistic study of pseudorotaxane formation via the slipping process targeting on nucleic acids2017

    • Author(s)
      鬼塚 和光, 千国 友子, 宮下 卓也, 永次 史
    • Organizer
      日本化学会 第97春季年会
    • Place of Presentation
      慶應大学(神奈川県横浜市)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
  • [Presentation] Spontaneous pseudorotaxane formation methods targeting on RNA2017

    • Author(s)
      K. Onizuka, T. Miyashita, T. Chikuni, F. Nagatsugi
    • Organizer
      The 43rd Naito conference on noncoding RNA: biology, chemistry, and diseases
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Spontaneous pseudorotaxane formation targeting RNA2017

    • Author(s)
      K. Onizuka, J. Matsuyama, T. Miyashita, Y. Kawasaki, K. Igawa, K. Tomooka, F. Nagatsugi
    • Organizer
      The second international symposium on biofunctional chemistry
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 翻訳制御を指向した擬ロタキサン形成オリゴ核酸の開発2016

    • Author(s)
      鬼塚 和光, 宮下 卓也, 永次 史
    • Organizer
      第2回日本核酸医薬学会年会
    • Place of Presentation
      東京理科大学(東京都葛飾区)
    • Year and Date
      2016-11-15
    • Related Report
      2016 Research-status Report
  • [Presentation] Structural optimization of pseudorotaxane-forming oligoDNA targeting on nucleic acids2016

    • Author(s)
      K. Onizuka, T. Miyashita, F. Nagatsugi
    • Organizer
      The 43th International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      熊本大学(熊本県熊本市)
    • Year and Date
      2016-09-27
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 標的核酸に対して自発的に擬ロタキサン構造を形成する人工核酸の開発2016

    • Author(s)
      鬼塚 和光, 宮下 卓也, 永次 史
    • Organizer
      第10回バイオ関連化学シンポジウム
    • Place of Presentation
      石川県立音楽堂(石川県金沢市)
    • Year and Date
      2016-09-07
    • Related Report
      2016 Research-status Report
  • [Remarks] 永次研究室ホームページ

    • URL

      http://www2.tagen.tohoku.ac.jp/lab/nagatsugi/html/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 永次研究室ホームページ

    • URL

      http://www.tagen.tohoku.ac.jp/labo/nagatsugi/

    • Related Report
      2017 Research-status Report 2016 Research-status Report

URL: 

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

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