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Development of antigene strategy by triplex forming oligonucleotides having artificial nucleoside analogues

Research Project

Project/Area Number 24689006
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Drug development chemistry
Research InstitutionKyushu University

Principal Investigator

TANIGUCHI YOSUKE  九州大学, 薬学研究科(研究院), 准教授 (00452714)

Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥26,910,000 (Direct Cost: ¥20,700,000、Indirect Cost: ¥6,210,000)
Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
Keywords核酸医薬 / アンチジーン核酸 / 人工核酸 / 遺伝子発現制御 / 核酸化学 / 3本鎖形成オリゴヌクレオチド / 3本鎖DNA形成オリゴヌクレオチド / ゲノム創薬 / 有機化学
Outline of Final Research Achievements

The triplex DNA formation against duplex DNA offers a potential basis for genome targeting technology and/or medicine with sequence specificity. In triplex DNA, the sequence-specificity is established via the formation of specific base triplets between a triplex forming oligonucleotide and a duplex DNA, however, there is no natural nucleoside which can recognize inverted sites. The application of the triplex formation is consequently limited to the homopurine-homopyrimidine region of a duplex DNA. We showed the design and synthesis of artificial nucleoside analogues for selective recognition of CG base pair to expand triplex-forming sequence. The 2’-deoxycytidine derivatives were shown to possess high selectivity and affinity toward CG base pair without being effected by neighboring bases. Furthermore, TFO bearing them was demonstrated to effectively inhibit gene expression in living cells.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (44 results)

All 2016 2015 2014 2013 2012 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Acknowledgement Compliant: 4 results) Presentation (32 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results) Remarks (3 results)

  • [Journal Article] Discrimination Between 8-Oxo-2'-Deoxyguanosine and 2'-Deoxyguanosine in DNA by the Single Nucleotide Primer Extension Reaction with Adap Triphosphate2015

    • Author(s)
      Taniguchi Y., Kikukawa Y and Sasaki S.
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 54 Pages: 5147-5151

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Enhancement of TFO Triplex Formation by Conjugation with Pyrene <i>via</i> Click Chemistry2015

    • Author(s)
      Taniguchi Y, Tomizaki A, Matsueda N, Okamura H, Sasaki S
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 63 Issue: 11 Pages: 920-926

    • DOI

      10.1248/cpb.c15-00570

    • NAID

      130005105722

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Remarkable acceleration of a DNA/RNA inter-strand functionality transfer reaction to modify a cytosine residue: the proximity effect via complexation with a metal cation2014

    • Author(s)
      Jitsuzaki D., Onizuka K., Nishimoto A., Oshiro I., Taniguchi Y. and Sasaki S
    • Journal Title

      Nucleic Acids Res

      Volume: 42 Issue: 13 Pages: 8808-8815

    • DOI

      10.1093/nar/gku538

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] An Isocytidine Derivative with a 2-Amino-6-methylpyridine Unit for Selective Recognition of the CG Interrupting Site in an Antiparallel Triplex DNA2014

    • Author(s)
      Hidenori Okamura, Yosuke Taniguchi and Shigeki Sasaki
    • Journal Title

      ChemBioChem

      Volume: 15 Issue: 16 Pages: 2374-2378

    • DOI

      10.1002/cbic.201402328

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Synthesis of 1'-phenyl-2-OMe ribose analogues connecting the thymine base at the 1' position through a flexible linker for the formation of a stable anti-parallele triplex DNA2013

    • Author(s)
      Taniguchi Y., Okamura H., Fujino N., Sasaki S.
    • Journal Title

      Tetrahedron

      Volume: 69(2) Issue: 2 Pages: 600-606

    • DOI

      10.1016/j.tet.2012.11.016

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-(Guanidinoethyl)-2'-deoxy-5-methylisocytidine exhibits selective recognition of a CG interrupting site for the formation of anti-parallel triplexes2013

    • Author(s)
      Hidenori Okamura, Yosuke Taniguchi and Shigeki Sasaki
    • Journal Title

      Organic and Biomolecular Chemistry

      Volume: 11 Issue: 23 Pages: 3918-3924

    • DOI

      10.1039/c3ob40472b

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient DNA strand displacement by a W-shaped nucleoside analogue (WNA-&#61538;T) containing an ortho-methyl-substituted phenyl ring2012

    • Author(s)
      Aoki E., Taniguchi Y., Wada Y., Sasaki S
    • Journal Title

      ChemBioChem,

      Volume: 13(8) Issue: 8 Pages: 1152-1160

    • DOI

      10.1002/cbic.201200066

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Properties of Oligonucleotidewith Phenyl-Substituted Carbocyclic Nucleoside Analogues for the Formation ofDuplex and Triplex DNA2012

    • Author(s)
      Nasr T, Taniguchi Y., Takaki T., Okamura H., Sasaki S.
    • Journal Title

      Nucleosides, Nucleotides and Nucleic Acids,

      Volume: 31(12) Issue: 12 Pages: 8441-860

    • DOI

      10.1080/15257770.2012.737970

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An efficient antigene activity and antiproliferative effect by targeting the Bcl-2 or survivin gene with triplex forming oligonucleotides containing a W-shaped nucleoside analogue (WNA-βT)2012

    • Author(s)
      Taniguchi, Y. and Sasaki, S.
    • Journal Title

      Org. Biomol. Chem

      Volume: 10 Issue: 41 Pages: 8336-8341

    • DOI

      10.1039/c2ob26431e

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 8-Oxoguanosine選択的なDNAポリメラーゼ基質としての非天然ヌクレオチドの開発2016

    • Author(s)
      菊川誉也、谷口陽祐、佐々木茂貴
    • Organizer
      日本薬学会第136回年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 損傷類似人工核酸による核酸修復酵素阻害剤の開発2016

    • Author(s)
      谷口陽祐
    • Organizer
      日本薬学会第136回年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Recognition and discrimination between 8-oxo-2'deoxyguanosin and 2'deoxyguanosine in DNA using the adenosine-1,3-diazaphenoxazine nucleoside derivatives2015

    • Author(s)
      Yosuke Taniguchi,Yoshiya Kikukawa, Shigeki Sasaki
    • Organizer
      PACIFICHEM2015
    • Place of Presentation
      ハワイ
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] Synthesis of novel pseudocytidine derivatives for the selective recognition of CG base pairs in triple-helix DNA2015

    • Author(s)
      Hidenori Okamura, Yosuke Taniguchi, Shigeki Sasaki
    • Organizer
      PACIFICHEM2015
    • Place of Presentation
      ハワイ
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] 非天然型3本鎖DNA形成を可能にする人工核酸の合成とアンチジーン法への応用2015

    • Author(s)
      谷口陽祐、岡村秀紀、佐々木茂貴
    • Organizer
      日本核酸医薬学会第1回年会
    • Place of Presentation
      京都
    • Year and Date
      2015-11-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] 酸化損傷塩基検出を目指したプリンヌクレオチド誘導体の合成と機能評価2015

    • Author(s)
      菊川誉也、谷口陽祐、佐々木茂貴
    • Organizer
      第45回複素環化学討論会
    • Place of Presentation
      早稲田大学
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] Synthesis and evaluationof 8-oxo-2'-deoxyguanosine analogues as the novel binding compound for DNArepair enzyme2015

    • Author(s)
      Mayuko Wada, Yizhen Yin,Shigeki Sasaki, Yosuke Taniguchi
    • Organizer
      第42回国際核酸化学シンポジウム
    • Place of Presentation
      姫路
    • Year and Date
      2015-09-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] DNA修復酵素に対する結合を目指した酸化損傷塩基類似体の合成と機能評価2015

    • Author(s)
      和田真由子、佐々木茂貴、谷口陽
    • Organizer
      第9回バイオ関連化学シンポジウム
    • Place of Presentation
      熊本
    • Year and Date
      2015-09-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] Development of adenosine derivatives modified with phenoxazine unit for the recognition of 8-oxo-2'-deoxyguanosine in DNA2015

    • Author(s)
      Yosuke Taniguchi
    • Organizer
      The 6th Japanese-Sino Symposium on Organic Chemistry for Young Scientists
    • Place of Presentation
      仙台
    • Year and Date
      2015-09-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of the 8-Halogenated-7-deazadG as an 8-Oxo-dG Analogue for the inhibition of their repair enzymes2015

    • Author(s)
      Yosuke Taniguchi
    • Organizer
      The 1st HU-TMU-KU Joint Symposium for Pharmaceutical Sciences、
    • Place of Presentation
      札幌
    • Year and Date
      2015-08-29
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 遺伝子修復酵素特異的結合を目指した酸化損傷塩基類似体の開発2015

    • Author(s)
      谷口陽祐、尹貽貞、和田真由子、佐々木茂貴
    • Organizer
      日本ケミカルバイオロジー学会第10回年会
    • Place of Presentation
      東北大学
    • Year and Date
      2015-06-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] 3本鎖DNA中のCG塩基対を選択的に認識する擬シチジン誘導体の合成と機能評価2015

    • Author(s)
      岡村秀紀、谷口陽祐、佐々木茂貴
    • Organizer
      第13回次世代を担う有機化学シンポジウム
    • Place of Presentation
      立命館大学
    • Year and Date
      2015-05-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] CG障害部位を選択的に認識する擬シチジン誘導体の合成と3本鎖形成能の評価2015

    • Author(s)
      岡村秀紀、谷口陽祐、佐々木茂貴
    • Organizer
      日本薬学会第135回年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Specific recognition of CG base pairs by novel pseudo-cytidine derivatives in antiparallel DNA triplexes2014

    • Author(s)
      Hidenori Okamura, Yosuke Taniguchi, Shigeki Sasaki
    • Organizer
      第41回国際核酸化学シンポジウム
    • Place of Presentation
      福岡
    • Year and Date
      2014-11-05 – 2014-11-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] Development of triplex-forming oligonucleotide having artificial nucleoside analogues to inhibit the gene expression as an antigene strategy2014

    • Author(s)
      Yosuke Taniguchi, Hidenori Okamura, Shigeki Sasaki
    • Organizer
      DPhG Jahrestagung 2014/ Annual meeting,
    • Place of Presentation
      Frankfurt, Deutsche
    • Year and Date
      2014-09-24 – 2014-09-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] CG塩基対を選択的に認識可能な擬シチジン誘導体の合成と3本鎖形成能評価2014

    • Author(s)
      岡村秀紀、谷口陽祐、佐々木茂貴
    • Organizer
      アンチセンスシンポジウム・遺伝子・デリバリーシンポジウム2014
    • Place of Presentation
      東京
    • Year and Date
      2014-09-08 – 2014-09-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Selective CG base pair recognition by pyrimidine nucleosideanalogues in all four flanking pairs within antiparallel triple helix DNA2014

    • Author(s)
      Hidenori Okamura, Yosuke Taniguchi, Shigeki Sasaki
    • Organizer
      XXI Round Table on Nucleosides, Nucleotides and Nucleic Acids
    • Place of Presentation
      POZNAN, POLAND.
    • Year and Date
      2014-08-24 – 2014-08-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] CG塩基対を安定かつ選択的に認識可能なN2-修飾イソシチジン誘導体の合成と3本鎖形成能の評価2014

    • Author(s)
      岡村秀紀、谷口陽祐、佐々木茂貴
    • Organizer
      日本薬学会第134回年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] CpGアイランド特異的に結合する人工核酸の開発2014

    • Author(s)
      松枝望、谷口陽祐、佐々木茂貴
    • Organizer
      日本薬学会第134回年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] CG塩基対を2ヶ所の水素結合部位で認識可能なイソシチジン誘導体の合成と3本鎖形成能の評価2013

    • Author(s)
      岡村秀紀
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2013-03-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] CG 塩基対を選択的に認識可能なN- グアニジノエチルイソシチジンの合成と3 本鎖DNA 形成能の評価2013

    • Author(s)
      岡村秀紀、谷口陽祐、佐々木茂貴
    • Organizer
      第50回化学関連支部合同九州大会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] N-(Guanidinoethyl)-2'-deoxy-5-methylisocytidine exhibits selective recognition of the CG inversion site for the formation of anti-parallel triplex DNA2013

    • Author(s)
      Hidenori Okamura, Yosuke Taniguchi, and Shigeki Sasaki
    • Organizer
      ACMS2013
    • Place of Presentation
      沖縄
    • Related Report
      2013 Annual Research Report
  • [Presentation] 3本鎖DNAの安定化を目指した新規1',1'-二置換ヌクレオシドの開発2013

    • Author(s)
      冨崎瑛、谷口陽祐、岡村秀紀、佐々木茂貴
    • Organizer
      第25回若手研究者のためのセミナー
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] CG塩基対を選択的に認識可能なN-修飾イソシチジン誘導体の合成と3本鎖形成能の評価2013

    • Author(s)
      岡村秀紀、谷口陽祐、佐々木茂貴
    • Organizer
      第25回若手研究者のためのセミナー
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] Synthesesand Evaluation of Anti-parallel Triplex Formation of 1’-Phenyl-2’-ThymineNucleoside Analogues for the Application to the Antigene Strategy2013

    • Author(s)
      Yosuke Taniguchi,Akira Tomizaki, Hidenori Okamura, Syohei Misumi, Tomoko Takaki, Naoto Ishibashi and Shigeki Sasaki
    • Organizer
      AIMECS2013
    • Place of Presentation
      台湾
    • Related Report
      2013 Annual Research Report
  • [Presentation] CpGアイランドを標的とした人工核酸の開発2013

    • Author(s)
      松枝望、谷口陽祐、佐々木茂貴
    • Organizer
      第30回日本薬学会九州支部大会
    • Place of Presentation
      長崎
    • Related Report
      2013 Annual Research Report
  • [Presentation] Synthesis and triplex DNA forming evaluation of 2' -deoxyisocytidine derivatives with two hydrogen-bonding sites2012

    • Author(s)
      Hidenori Okamura
    • Organizer
      2nd Junior ICCEOCA
    • Place of Presentation
      University of Malaya
    • Year and Date
      2012-12-10
    • Related Report
      2012 Annual Research Report
  • [Presentation] 3本鎖DNAを安定化させる新規人工核酸の合成と評価2012

    • Author(s)
      冨崎瑛
    • Organizer
      第29回日本薬学会九州支部大会
    • Place of Presentation
      熊本大学薬学部
    • Year and Date
      2012-12-09
    • Related Report
      2012 Annual Research Report
  • [Presentation] Triplex-forming properties of the oligodeoxynucleot ides containing isocytidine derivatives with two hydrogenbonding sites against CG base pair2012

    • Author(s)
      Hidenori Okamura
    • Organizer
      第39回国際核酸化学シンポジウム
    • Place of Presentation
      名古屋大学豊田講堂
    • Year and Date
      2012-11-16
    • Related Report
      2012 Annual Research Report
  • [Presentation] Effective Strand Exchange Reaction Caused by a New W-shaped Nucleoside Analog (oMe-WNA-bT)2012

    • Author(s)
      Eriko Aoki,
    • Organizer
      第39回国際核酸化学シンポジウム
    • Place of Presentation
      名古屋大学豊田講堂
    • Year and Date
      2012-11-16
    • Related Report
      2012 Annual Research Report
  • [Presentation] CG塩基対を認識可能な2ヶ所の水素結合サイトを有するイソシチジン誘導体の3本鎖DNA形成能評価2012

    • Author(s)
      岡村秀紀
    • Organizer
      アンチセンス遺伝子デリバリーシンポジウム2 0 12
    • Place of Presentation
      仙台市民会館
    • Year and Date
      2012-09-25
    • Related Report
      2012 Annual Research Report
  • [Presentation] オルト位にメチル基を持つWNA誘導体によるDNA鎖交換反応促進作用の機構解明2012

    • Author(s)
      谷口陽祐
    • Organizer
      第6回バイオ関連化学シンポジウム
    • Place of Presentation
      北海道大学
    • Year and Date
      2012-09-07
    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://bioorg.phar.kyushu-u.ac.jp/index.html

    • Related Report
      2015 Annual Research Report
  • [Remarks]

    • URL

      http://bioorg.phar.kyushu-u.ac.jp/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 九州大学薬学研究院 生物有機合成化学分野

    • URL

      http://bioorg.phar.kyushu-u.ac.jp/index.html

    • Related Report
      2013 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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