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Elucidation of pharmacological effects of antibiotics against genetic diseases caused by nonsense mutations and development of new therapeutic agents

Research Project

Project/Area Number 26860025
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Physical pharmacy
Research InstitutionSophia University

Principal Investigator

Kondo Jiro  上智大学, 理工学部, 准教授 (10546576)

Research Collaborator Hanessian Stephen  モントリオール大学, 教授
Baasov Timor  テクニオン・イスラエル工科大学, 教授
Ennifar Eric  フランス国立科学研究機構, 研究部長
Auffinger Pascal  フランス国立科学研究機構, 研究部長
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsナンセンス変異型遺伝性疾患 / 抗生物質 / リボソーム / X線結晶解析 / ドラッグデザイン
Outline of Final Research Achievements

In order to develop new therapeutic agents against genetic diseases, I have performed structural studies of the ribosomal RNA molecular switches of several different organisms/cells by X-ray analysis and have designed and synthesized new drug compounds based on the obtained structural data. We have succeeded to design and synthesize several compounds possessing high readthrough, antiprotozoal or antibacterial activity and less toxicity against human. Especially, one of the designed/synthesized fluorinated aminoglycosides specifically binds to the RNA molecular switches of eukaryote and antibiotic-resistant bacteria. This compound can be a potent therapeutic agent against genetic diseases caused by nonsense mutations.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (28 results)

All 2016 2015 2014 Other

All Int'l Joint Research (5 results) Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Open Access: 3 results,  Peer Reviewed: 2 results,  Acknowledgement Compliant: 2 results) Presentation (14 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] モントリオール大学(カナダ)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] テクニオン・イスラエル工科大学(イスラエル)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] ストラスブール大学(フランス)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] モントリオール大学(カナダ)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] テクニオン・イスラエル工科大学(イスラエル)

    • Related Report
      2015 Research-status Report
  • [Journal Article] DNAナノメディシンのStructure-Based Design2016

    • Author(s)
      近藤次郎
    • Journal Title

      月刊化学工業

      Volume: 27 Pages: 28-36

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 核酸構造生物学の最前線2016

    • Author(s)
      近藤次郎
    • Journal Title

      SOPHIA SCI-TECH 上智大学理工学振興会会報

      Volume: 27 Pages: 2-7

    • Related Report
      2015 Research-status Report
  • [Journal Article] ノンコーディング核酸の「動き」を見て「働き」を理解する2015

    • Author(s)
      近藤次郎
    • Journal Title

      日本RNA学会会報

      Volume: 36 Pages: 12-14

    • Related Report
      2015 Research-status Report
    • Open Access
  • [Journal Article] Crystallographic studies of the ribosomal A-site molecular switches by using model RNA oligomers2015

    • Author(s)
      Jiro Kondo
    • Journal Title

      Nucleic Acid Crystallography: Methods and Protocols (Methods in Molecular Biology)

      Volume: 1320 Pages: 315-327

    • DOI

      10.1007/978-1-4939-2763-0_20

    • ISBN
      9781493927623, 9781493927630
    • Related Report
      2015 Research-status Report
  • [Journal Article] Crystal structure of the bacterial A site in complex with axial 4’-fluoro neomycin analog2015

    • Author(s)
      Hiroki Kanazawa, Stephen Hanessian, Jiro Kondo
    • Journal Title

      Photon Factory Activity Report 2014

      Volume: 32 Pages: 231-231

    • Related Report
      2015 Research-status Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Crystal Structure of the Bacterial A Site in Complex with β-Fluoro Neomycin Analog2015

    • Author(s)
      Hiroki Kanazawa, Juan Pablo Maianti, Stephen Hanessian, Jiro Kondo
    • Journal Title

      Photon Factory Activity Report 2014

      Volume: 32 Pages: 232-232

    • Related Report
      2015 Research-status Report
    • Open Access / Int'l Joint Research
  • [Journal Article] 核酸構造生物学の創薬・ナノ材料科学への展開2015

    • Author(s)
      近藤次郎
    • Journal Title

      日本化学会・生体機能関連化学部会ニュースレター

      Volume: 29 Pages: 15-18

    • Related Report
      2014 Research-status Report
  • [Journal Article] Toxicity modulation, resistance enzyme evasion, and A-site X-ray structure of broad-spectrum antibacterial neomycin analogs2014

    • Author(s)
      Juan Pablo Maianti, Hiroki Kanazawa, Paola Dozzo, Rowena D. Matias, Lee Ann Feeney, Eliana S. Armstrong, Darin J. Hildebrandt, Timothy R. Kane, Micah J. Gliedt, Adam A. Goldblum, Martin S. Linsell, James B. Aggen, Jiro Kondo, Stephen Hanessian.
    • Journal Title

      ACS Chemical Biology

      Volume: 9 Issue: 9 Pages: 2067-2073

    • DOI

      10.1021/cb5003416

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Synthesis, broad spectrum antibacterial activity, and X-ray co-crystal structure of the decoding bacterial ribosomal A-site with 4'-deoxy-4'-fluoro neomycin analogs2014

    • Author(s)
      Stephen Hanessian, Oscar M. Saavedra, Miguel A. Vilchis-Reyes, Juan P. Maianti, Hiroki Kanazawa, Paola Dozzo, Rowena D. Matias, Alisa Serio, Jiro Kondo.
    • Journal Title

      Chemical Science

      Volume: 5 Issue: 12 Pages: 4621-4632

    • DOI

      10.1039/c4sc01626b

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Crystal structures of the bacterial ribosomal RNA in complex with fluorinated aminoglycosides2016

    • Author(s)
      Hiroki Kanazawa, Juan P. Maianti, Stephen Hanessian, Jiro Kondo
    • Organizer
      ISNAC2016
    • Place of Presentation
      熊本大学黒髪キャンパス(熊本市)
    • Year and Date
      2016-09-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DNAナノマテリアル・ナノメディシンのStructure-Based Design2016

    • Author(s)
      近藤次郎
    • Organizer
      JST 新技術説明会
    • Place of Presentation
      JST東京本部別館ホール(東京都千代田区)
    • Year and Date
      2016-09-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] Interactions between the bacterial ribosomal RNA and fluorinated aminoglycosides2016

    • Author(s)
      Hiroki Kanazawa, Juan P. Maianti, Stephen Hanessian, Jiro Kondo
    • Organizer
      RNA2016
    • Place of Presentation
      京都国際会館(京都市)
    • Year and Date
      2016-06-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] フッ素化アミノグリコシドの細菌リボソームRNAとの相互作用2015

    • Author(s)
      金澤宏樹、Juan Pablo Maianti、Stephen Hanessian、近藤次郎
    • Organizer
      日本核酸医薬学会 第1回年会
    • Place of Presentation
      京都テルサ(京都府京都市)
    • Year and Date
      2015-11-30
    • Related Report
      2015 Research-status Report
  • [Presentation] フッ素化アミノグリコシドとリボソームRNAの複合体のX線結晶解析2015

    • Author(s)
      金澤宏樹、Juan Pablo Maianti、Stephen Hanessian、近藤次郎
    • Organizer
      GE Life Sciences Day 2015
    • Place of Presentation
      パシフィコ横浜会議センター(神奈川県横浜市)
    • Year and Date
      2015-07-24
    • Related Report
      2015 Research-status Report
  • [Presentation] RNA-リガンド相互作用の分類2015

    • Author(s)
      近藤次郎、Eric Westhof
    • Organizer
      GE Life Sciences Day 2015
    • Place of Presentation
      パシフィコ横浜会議センター(神奈川県横浜市)
    • Year and Date
      2015-07-24
    • Related Report
      2015 Research-status Report
  • [Presentation] 核酸塩基-アミノ酸相互作用の分類2015

    • Author(s)
      近藤次郎、Eric Westhof
    • Organizer
      GE Life Sciences Day 2015
    • Place of Presentation
      パシフィコ横浜会議センター(神奈川県横浜市)
    • Year and Date
      2015-07-24
    • Related Report
      2015 Research-status Report
  • [Presentation] フッ素を導入した新規アミノグリコシドと細菌リボソームRNAの複合体のX線結晶解析2015

    • Author(s)
      金澤宏樹、Juan Pablo Maianti、Stephen Hanessian、近藤次郎
    • Organizer
      第3回物構研サイエンスフェスタ
    • Place of Presentation
      つくば国際会議場(つくば市)
    • Year and Date
      2015-03-17 – 2015-03-18
    • Related Report
      2014 Research-status Report
  • [Presentation] Crystal structure of RNA duplex containing strontium ion binding motif2014

    • Author(s)
      Hiroki Kanazawa, Jiro Kondo
    • Organizer
      ISNAC2014 (The 41th International Symposium on Nucleic Acid Chemistry)
    • Place of Presentation
      北九州国際会議場(北九州市)
    • Year and Date
      2014-11-05 – 2014-11-07
    • Related Report
      2014 Research-status Report
  • [Presentation] Crystal structures of the bacterial ribosomal A site containing an antibiotic-resistant mutation2014

    • Author(s)
      Fumika Baba, Mai Koganei, Jiro Kondo
    • Organizer
      ISNAC2014 (The 41th International Symposium on Nucleic Acid Chemistry)
    • Place of Presentation
      北九州国際会議場(北九州市)
    • Year and Date
      2014-11-05 – 2014-11-07
    • Related Report
      2014 Research-status Report
  • [Presentation] Structural and crystal polymorphisms of the mitochondrial ribosomal A-site RNA2014

    • Author(s)
      Mai Miyazaki, Tamaki Tetsumoto, Yukiko Takahashi, Jiro Kondo
    • Organizer
      ISNAC2014 (The 41th International Symposium on Nucleic Acid Chemistry)
    • Place of Presentation
      北九州国際会議場(北九州市)
    • Year and Date
      2014-11-05 – 2014-11-07
    • Related Report
      2014 Research-status Report
  • [Presentation] フッ素を導入した新規アミノグリコシドの細菌リボソームRNAへの結合様式の解明2014

    • Author(s)
      金澤宏樹、Juan Pablo Maianti、Stephen Hanessian、近藤次郎
    • Organizer
      平成26年度日本結晶学会年会
    • Place of Presentation
      東京大学(東京都)
    • Year and Date
      2014-11-01 – 2014-11-03
    • Related Report
      2014 Research-status Report
  • [Presentation] Crystal structure of unusual RNA duplex containing strontium ion binding motif2014

    • Author(s)
      Hiroki Kanazawa, Jiro Kondo
    • Organizer
      IUCr2014 (23rd Congress and General Assembly of International Union of Crystallography
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      2014-08-05 – 2014-08-12
    • Related Report
      2014 Research-status Report
  • [Presentation] フッ素を導入した新規アミノグリコシドとリボソームRNAの複合体のX線結晶解析2014

    • Author(s)
      金澤宏樹、Juan Pablo Maianti、Stephen Hanessian、近藤次郎
    • Organizer
      第16回日本RNA学会年会
    • Place of Presentation
      ウィンクあいち(名古屋市)
    • Year and Date
      2014-07-23 – 2014-07-25
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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