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The new strategy for the development of the inhibitor of reverse transcriptase

Research Project

Project/Area Number 15K14975
Research Category

Grant-in-Aid for Challenging Exploratory Research

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

Principal Investigator

Nagatsugi Fumi  東北大学, 多元物質科学研究所, 教授 (90208025)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords逆転写阻害核酸系薬剤 / 薬剤耐性機構 / HIV治療薬 / ヌクレオチド除去反応 / 架橋反応 / ウイルスRNA
Outline of Final Research Achievements

A number of nucleoside (or nucleotide) reverse transcriptase inhibitors (NRTIs) are used in the treatment of HIV and hepatitis B. The long term administration of these medicines is required in this treatment, and leads the appearance of the drug-resistance virus. The major mechanism of resistance to NRTIs is a nucleotide excision, in which is removed of chain-terminating 3’-terminal NRTIs. In this study, we aim to develop the new strategy for the design of the reverse transcriptase inhibitor with drug resistance. We expected that the cross-linking reactions between RNA template and primer DNA would lead the inhibition for the reverse transcriptase reaction by forming covalent bond. We prepared the crosslink forming oligonucleotide (CFO) containing 2-amino-6-vinylpurine (AVP) at 3’ terminal position of the DNA primer. The CFO can react to the target thymine at the complementary site. The crosslinked duplex DNA can inhibit the HIV-1 reverse transcriptase by capturing this enzyme.

Report

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

    (49 results)

All 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Acknowledgement Compliant: 3 results,  Open Access: 3 results) Presentation (41 results) (of which Int'l Joint Research: 18 results,  Invited: 8 results) Remarks (1 results)

  • [Int'l Joint Research] Department of Chemistry/University of California(米国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Synthesis and properties of Cross-linkable DNA duplex using 4-Amino-2-Oxo-6-vinyl-1,3,5-Triazine2017

    • Author(s)
      Yamada,K.; Ishiyama,S.; Onizuka,K.; Nagatsugi,F.
    • Journal Title

      Tetrahedron

      Volume: 73 Issue: 11 Pages: 1424-1435

    • DOI

      10.1016/j.tet.2017.01.043

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / 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 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [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
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Synthesis of peptide nucleic acids (PNA) with a crosslinking agent to RNA and effective inhibition of dicer2016

    • Author(s)
      Akisawa Takuya, Yamada Ken, Nagatsugi Fumi
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 26 Issue: 24 Pages: 5902-5906

    • DOI

      10.1016/j.bmcl.2016.11.002

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Crosslinking reactions of 4-amino-6-oxo-2-vinylpyrimidine with guanine derivatives and structural analysis of the adducts2015

    • Author(s)
      S.Kusano, S. Ishiyama,Sik Lok Lam, T. Mashima, M. Katahira, K. Miyamoto, M. Aida, F. Nagatsugi
    • Journal Title

      Nucl.Acids Res

      Volume: 43 Issue: 16 Pages: 7717-7730

    • DOI

      10.1093/nar/gkv797

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Synthesis of Peptide Nucleic Acids Containing a Crosslinking Agent and Evaluation of Their Reactivities.2015

    • Author(s)
      T. Akisawa, Y. Ishizawa, F. Nagatsugi
    • Journal Title

      Molecules

      Volume: 20 Issue: 3 Pages: 4708-4719

    • DOI

      10.3390/molecules20034708

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 核酸高次構造をアルキル化する中分子の開発2017

    • Author(s)
      永次 史
    • Organizer
      日本薬学会第137年会(仙台)
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
    • Invited
  • [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(仙台)
    • Place of Presentation
      東北大学川内キャンパス(宮城県仙台市)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 脱塩基部位を持つ2本鎖DNAを標的とした効率的アルキル化プローブの開発2017

    • Author(s)
      丹野 宏亮・山田 研・佐々木 欣宏・佐藤 憲大・鬼塚 和光・永次 史
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      慶應義塾大学 日吉キャンパス(神奈川県横浜市)
    • Year and Date
      2017-03-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] Mechanistic study of pseudorotaxane formation via the slipping process targeting on nucleic acids2017

    • Author(s)
      ONIZUKA, Kazumitsu; CHIKUNI, Tomoko; MIYASHITA, Takuya; NAGATSUGI, Fumi
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      慶應義塾大学 日吉キャンパス(神奈川県横浜市)
    • Year and Date
      2017-03-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] Investigation of linker structures to functionalize pseudorotaxane-forming oligo nucleic acid2017

    • Author(s)
      TAGUCHI, Akifumi; ONIDUKA, Kazumitu; MIYASHITA, Takuya; NAGATSUGI, Fumi
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      慶應義塾大学 日吉キャンパス(神奈川県横浜市)
    • Year and Date
      2017-03-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] Selective G-quadruplex alkylation by vinyl triazine derivatives2017

    • Author(s)
      HAZEMI, Madoka Eurika; USAMI, Akira; KOBAYASHI, Tomohito; SATO, Norihiro; ONIZUKA, Kazumitsu; NAGATSUGI, Fumi
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      慶應義塾大学 日吉キャンパス(神奈川県横浜市)
    • Year and Date
      2017-03-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] Development of the Chemical Tools for the Alkylation to Nucleic Acid Binding Protein2017

    • Author(s)
      F. Nagatsugi, K. Odaira, K. Yamada
    • Organizer
      Asian Chemical Biology Initiative (ACBI) 2017
    • Place of Presentation
      Ho-chi-minh, Vietnam
    • Year and Date
      2017-01-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of the Chemical Tools for the Alkylation to Nucleic Acid Binding Protein2016

    • Author(s)
      F. Nagatsugi, K. Odaira, K. Yamada
    • Organizer
      The Fourth Asian Chemical Biology Conference (ACBC2016)
    • Place of Presentation
      85 Sky Tower Hotel, Kaohsiung, TAIWAN
    • Year and Date
      2016-11-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Synthesis of Middle Molecular Probes for the Selective Chemical Modification to Higher-Order Structures in RNA2016

    • Author(s)
      A. Usami, T. Kobayashi, M. E. Hazemi, N. Sato, K. Onizuka, F. Nagatsugi
    • Organizer
      ISONIS 10
    • Place of Presentation
      Hyogo, Awajishima-shi,  yumebtai international conference center
    • Year and Date
      2016-11-18
    • Related Report
      2016 Annual Research 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
      東京理科大学葛飾キャンパス図書館大ホール(東京都葛飾区)
    • Year and Date
      2016-11-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] Structural optimization of pseudorotaxane-forming oligoDNA targeting on nucleic acids2016

    • Author(s)
      K. Onizuka, Miyashita, T., F. Nagatsugi
    • Organizer
      The 43th International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      Kumamoto univ., Kuamamoto, Japan
    • Year and Date
      2016-09-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Synthesis of natural-like cross-linked duplex RNA and its properties2016

    • Author(s)
      M.E. Hazemi, K. Onizuka, K. Yamada, F. Nagatsugi
    • Organizer
      The 43th International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      Kumamoto univ., Kumamoto, Japan
    • Year and Date
      2016-09-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Preparation of “Cross-Linkable duplex” using the Oligonucleotide Containing 4-amino-2-oxo-6-vinyl-1,3,5-triazine2016

    • Author(s)
      F. Nagatsugi, K. Odaira, K. Yamada
    • Organizer
      The First A3 Roundtable Meeting on Chemical Probe Research Hub
    • Place of Presentation
      Hotel LEOPALACE Hakata, Fukuoka Japan
    • Year and Date
      2016-09-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [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
      石川県立音楽堂もてなしドーム(石川県金沢市)
    • Year and Date
      2016-09-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] U-Uミスマッチ構造選択的な化学修飾を目指した中分しプローブの開発2016

    • Author(s)
      宇佐美 彬、小林 倫仁、Hazemi Eurika Madoka、鬼塚 和光、永次 史
    • Organizer
      第10回バイオ関連化学シンポジウム
    • Place of Presentation
      石川県立音楽堂もてなしドーム(石川県金沢市)
    • Year and Date
      2016-09-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] Development of Middle Molecular Probes for the Selective Chemical Modification to Higher-Order Structures in RNA2016

    • Author(s)
      A. Usami, T. Kobayashi, M. E. Hazemi, N. Sato, K. Onizuka, F. Nagatsugi
    • Organizer
      Tohoku University Campus Asia Program Summer School 2016
    • Place of Presentation
      Tohoku Univ. Sendai, Japan
    • Year and Date
      2016-08-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Deveropment of psedorotaxane-forming oligonucleotides aiming at translational regulation2016

    • Author(s)
      T. Miyashita, K. Onizuka, F. Nagatsugi
    • Organizer
      Tohoku University Campus Asia Program Summer School 2016
    • Place of Presentation
      Tohoku Univ. Sendai, Japan
    • Year and Date
      2016-08-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Synthesis of a new cross-linkable nucleic acid derivative targeting nucleic acid binding proteins2016

    • Author(s)
      K. Odaira, S. Ishiyama, K. Yamada, F. Nagatsugi
    • Organizer
      Tohoku University Campus Asia Program Summer School 2016
    • Place of Presentation
      Tohoku Univ. Sendai, Japan
    • Year and Date
      2016-08-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Synthesis of Natural-like Cross-linked duplex RNA for Biochemical Studies2016

    • Author(s)
      M. H. Eurika, K. Onizuka, K. Yamada, F. Nagatsugi
    • Organizer
      Tohoku University Campus Asia Program Summer School 2016
    • Place of Presentation
      Tohoku Univ. Sendai, Japan
    • Year and Date
      2016-08-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Synthesis of the middle-size molecules for alkylation to highly ordered structures of nucleic acids2016

    • Author(s)
      N. Sato, Y. Sasaki, G.Tsuji, A.Usami, K. Onizuka, K.Yamada and F. Nagatsugi
    • Organizer
      XXII Round Table on Nucleosides, Nucleotides and Nucleic Acids Chemical Biology of Nucleic Acids
    • Place of Presentation
      Paris, France
    • Year and Date
      2016-07-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Synthesis of a New Cross-Linkable Oligonucleotides having 4-Amino-6-Oxo-2-Vinyl-Triazine2016

    • Author(s)
      K. Yamada, K. Odaira, S. Ishiyama, F. Nagatsugi
    • Organizer
      XXII Round Table on Nucleosides, Nucleotides and Nucleic Acids Chemical Biology of Nucleic Acids
    • Place of Presentation
      Paris, France
    • Year and Date
      2016-07-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 核酸結合性蛋白質との架橋反応を目指したビニルトリアジン誘導体の開発2016

    • Author(s)
      山田 研、小平 健太、石山 翔午、鬼塚和光、永次 史
    • Organizer
      日本ケミカルバイオロジー学会 第11回年会
    • Place of Presentation
      京都テルサ(京都府京都市)
    • Year and Date
      2016-06-10
    • Related Report
      2016 Annual Research Report
  • [Presentation] DNA/RNAを標的とした擬ロタキサン形成オリゴDNAの構造最適化2016

    • Author(s)
      宮下 卓也、鬼塚 和光、永次 史
    • Organizer
      日本ケミカルバイオロジー学会 第11回年会
    • Place of Presentation
      京都テルサ(京都府京都市)
    • Year and Date
      2016-06-10
    • Related Report
      2016 Annual Research Report
  • [Presentation] Selective Reactions to Nucleic Acids with Higher Ordered Structure2016

    • Author(s)
      F. Nagatsugi, N. Sato, Kobayashi, Y. Sasaki, K.Onizuka, K. Yamada
    • Organizer
      12 th International, Symposium on Organic Reactions
    • Place of Presentation
      Kyoto Terrsa, Kyoto, Japan
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 核酸結合性蛋白質を標的とした新規架橋反応性核酸誘導体の合成2016

    • Author(s)
      小平健太、石山 翔午、山田 研、永次 史
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学、京都
    • Year and Date
      2016-03-24
    • Related Report
      2015 Research-status Report
  • [Presentation] 架橋2重鎖を用いた酵素的DNA伸長反応の阻害2016

    • Author(s)
      山田 研、永次 史
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学、京都
    • Year and Date
      2016-03-24
    • Related Report
      2015 Research-status Report
  • [Presentation] 核酸結合性タンパク質を標的とした新規架橋反応性塩基の合成と評価2016

    • Author(s)
      小平 健太、石山 翔午、山田 研、永次 史
    • Organizer
      第27回万有シンポジウム
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 脱塩基部位を持つ2本鎖DNA選択的アルキル化プローブの開発2016

    • Author(s)
      丹野宏亮、山田 研、佐々木欣宏、佐藤憲大、永次 史
    • Organizer
      第16回多元物質科学研究所研究発表会
    • Place of Presentation
      東北大学片平キャンパス・さくらホール(宮城県仙台市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Development of the Middle-size Molecules for Alkylation to Highly Ordered Structures of Nucleic Acids2016

    • Author(s)
      F. Nagatsugi
    • Organizer
      The 2nd International Symposium on Middle Molecular Strategy
    • Place of Presentation
      Senri Life Science Center, Osaka, Japan
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 架橋反応性塩基を持つ擬相補的PNAの合成と2本鎖DNAに対する反応性評価2015

    • Author(s)
      永次 史,秋澤拓也
    • Organizer
      第1回日本核酸医薬学会年会
    • Place of Presentation
      京都テルサ、京都
    • Year and Date
      2015-11-30
    • Related Report
      2015 Research-status Report
  • [Presentation] Development of the crosslinking reactions to RNA for application in cells2015

    • Author(s)
      Fumi Nagatsugi
    • Organizer
      Pharmaceutical Science Symposium 2015
    • Place of Presentation
      Sakura Hall, Sendai, Japan
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of the Effective Chemical Strategy for Regulation of Gene Expression2015

    • Author(s)
      Nagatsugi F., Hagihara S., Kusano S.
    • Organizer
      Pharmaceutical Science Symposium 2015
    • Place of Presentation
      Sakura Hall, Sendai, Japan
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 核酸結合性タンパク質との架橋反応を目指したビニルトリアジン誘導体の合成2015

    • Author(s)
      小平健太、石山翔午、山田研、 鬼塚和光、永次史
    • Organizer
      第4回CSJ化学フェスタ2015
    • Place of Presentation
      タワーホール船堀、東京
    • Year and Date
      2015-10-14
    • Related Report
      2015 Research-status Report
  • [Presentation] Development of the selective crosslinking reactions to 8-oxoguanine2015

    • Author(s)
      Fumi Nagatsugi, Shuhei Kusano, Shogo Ishiyama, Sik Lok Lam, Tsukasa Mashima, Masato Katahira, Fumi Nagatsugi
    • Organizer
      The 42th International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      Egret Himeji, Himeji, Japan
    • Year and Date
      2015-09-23
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 効率的遺伝子発現制御を目指した選択的化学反応の開発2015

    • Author(s)
      永次 史
    • Organizer
      第32回有機合成セミナー
    • Place of Presentation
      ウェルシティー湯河原、湯河原、神奈川県
    • Year and Date
      2015-09-15
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 核酸結合性蛋白質との反応を目指したビニルトリアジンを有する核酸誘導体の開発2015

    • Author(s)
      山田 研、石山 翔午、鬼塚 和光、永次 史
    • Organizer
      第9回バイオ関連化学シンポジウム
    • Place of Presentation
      熊本大学工学部 熊本
    • Year and Date
      2015-09-10
    • Related Report
      2015 Research-status Report
  • [Presentation] 生化学ツールのための架橋形成した天然擬似2本鎖RNAの合成2015

    • Author(s)
      鬼塚和光、Hazemi Madoka Eurika、永次 史、
    • Organizer
      第9回バイオ関連化学シンポジウム
    • Place of Presentation
      熊本大学工学部 熊本
    • Year and Date
      2015-09-10
    • Related Report
      2015 Research-status Report
  • [Presentation] Synthesis and Evaluation of the Reactivity of 7-Deaza-6-vinylguanosine Derivatives,2015

    • Author(s)
      Yusuke Abe, Ken Yamada, Yuta Ida, and Fumi Nagatsugi
    • Organizer
      Tohoku University Campus Asia Program Summer School
    • Place of Presentation
      Sendai, Japan
    • Year and Date
      2015-08-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 遺伝子の発現を効率よく制御可能な架橋反応性ペプチド核酸(PNA)の開発2015

    • Author(s)
      秋澤 拓也、永次 史
    • Organizer
      日本ケミカルバイオロジー学会 第11回年会
    • Place of Presentation
      東北大学 川内萩ホール
    • Year and Date
      2015-06-10
    • Related Report
      2015 Research-status Report
  • [Presentation] 核酸結合性蛋白質との架橋反応を目指したビニルトリアジン誘導体の開発2015

    • Author(s)
      山田 研、石山 翔午、鬼塚和光、永次 史
    • Organizer
      日本ケミカルバイオロジー学会 第11回年会
    • Place of Presentation
      東北大学 川内萩ホール
    • Year and Date
      2015-06-10
    • Related Report
      2015 Research-status Report
  • [Presentation] 架橋反応性ペプチド核酸(PNA)を用いた遺伝子発現制御法の開発2015

    • Author(s)
      秋澤 拓也、永次 史
    • Organizer
      第26回万有シンポジウム
    • Place of Presentation
      仙台国際センター、仙台市
    • Year and Date
      2015-06-06
    • Related Report
      2015 Research-status Report
  • [Remarks]

    • URL

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

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2022-02-16  

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