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Development of artificial nucleic acid conjugates as base materials for genome-based drug discovery and DNA-based diagnostics

Research Project

Project/Area Number 19390030
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Drug development chemistry
Research InstitutionOsaka University

Principal Investigator

IMANISHI Takeshi  Osaka University, 名誉教授 (40028866)

Co-Investigator(Kenkyū-buntansha) DOI Takefumi  大阪大学, 大学院・薬学研究科, 教授 (00211409)
KODAMA Tetsuya  大阪大学, 大学院・薬学研究科, 助教 (00432443)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2008: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2007: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
Keywordsゲノム創薬 / 人工核酸 / 遺伝子検出 / 遺伝子診断 / DNA
Research Abstract

ライフサイエンス領域での基盤材料となる人工核酸として、これまでにない新しい架橋構造を持つ架橋型人工核酸(BNA)を種々設計し、その合成法を確立した。また、新しい蛍光分子やDNAアルキル化分子を創製するとともに更なる誘導体化を実施し、核酸との複合体化を可能とした。さらに、核酸イメージング技術や送達法等への応用が期待できる核酸の別機能性分子との効率的複合体化法の開発に成功した。複合体化BNAの遺伝子発現抑制活性を評価し、血清中での高い安定性や、培養細胞内での高い遺伝子発現抑制能を見いだした。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (36 results)

All 2009 2008 2007

All Journal Article (16 results) (of which Peer Reviewed: 14 results) Presentation (20 results)

  • [Journal Article] A Bridged Nucleic Acid, 2',4'-BNA^<COC> : Synthesis of Fully Modified Oligonucleotides Bearing Thymine, 5-Methylcytosine, Adenine and Guanine 2',4'-BNA^<COC> Monomers, and RNA-selective Nucleic Acid Recognition2009

    • Author(s)
      Yasunori Mitsuoka, Tetsuya Kodama, Ryo Ohnishi, Yoshiyuki Hari, Takeshi Imanishi and Satoshi Obika
    • Journal Title

      Nucleic Acids Res 37

      Pages: 1225-1238

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Design, Synthesis, and Evaluation of a Novel Bridged Nucleic Acid, 2',5'-BNA ^<ON> with S-type Sugar Conformation Fixed by N-O Linkage2009

    • Author(s)
      Tetsuya Kodama, Chieko Matsuo, Hidetsugu Ori, Tetsuya Miyoshi, Satoshi Obika, Kazuyuki Miyashita, Takeshi Imanishi
    • Journal Title

      Tetrahedron 65

      Pages: 2116-2123

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of a Novel trans-3',4'-BNA Monomer Bearing a 4,8-Dioxa-5-azabicyclo-[5.3.0]decane Skeleton2009

    • Author(s)
      Tetsuya Kodama, Kensaku Sugaya, Takeshi Baba, Takeshi Imanishi, Satoshi Obika
    • Journal Title

      Heterocycles 79

      Pages: 873-882

    • NAID

      40016543114

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of a novel trans-3', 4' -BNA monomer bearinga 4, 8-dioxa-5-azabicyclo[5. 3. 0]decane skeleton.2009

    • Author(s)
      Tetsuya Kodama
    • Journal Title

      Heterocycles 79(印刷中)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and properties of 2 ' -deoxy-trans-3', 4' -BNA with S-type sugar puckering.2009

    • Author(s)
      Tetsuya Kodama
    • Journal Title

      Heterocycles 77

      Pages: 1209-1217

    • NAID

      40016454354

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic stabilization of nucleic acid assembly by 2' - 0, 4' -C-methylene bridged nucleic acid modification and additions of Comb-type cat ionic copolymers.2009

    • Author(s)
      Hidetaka Torigoe
    • Journal Title

      Biochemistry 48(印刷中)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A bridged nucleic acid, 2', 4'-BNACOC : Synthesis of fullymodified oligonucleotides bearing thymine, 5-methylcyto-sine, adenine and guanine 2', 4'-BNAC0C monomers, andRNA-selective nucleic acid recognition.2009

    • Author(s)
      Yasunori Mitsuoka
    • Journal Title

      Nucleic Acids Res. 37

      Pages: 1225-1238

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design, synthesis, and evaluation of a novel bridgednucleic acid, 2′, 5′ -BNA^ON, with S-type sugarconformation fixed by N-O linkage.2009

    • Author(s)
      Te tsuya Kodama
    • Journal Title

      Tetrahedron 65

      Pages: 2116-2123

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and properties of 3'-amino-2',4'-BNA, a bridged nucleic acid with a N3'-P5' phosphoramidate linkage. Bioorg2008

    • Author(s)
      Satoshi Obika, S.M.Abdur Rahman, Bingbing Song, Mayumi Onoda, Makoto Koizumi, Koji Morita, Takeshi Imanishi
    • Journal Title

      Med. Chem 16

      Pages: 9230-9237

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Design, synthesis and properties of 2',4'-BNA ^<NC> : A bridged nucleic acid analogue2008

    • Author(s)
      S. M. Abdur. Rahman, Sayori. Seki, Satoshi. Obika, Haruhisa Yoshikawa, Kazuyuki Miyashita, Takeshi Imanishi
    • Journal Title

      J. Am. Chem. Soc. 130

      Pages: 4886-4896

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Systematic analysis of enzymatic DNA polymferizationusing oligo-DNA templates and triphosphate analogsinvolving 2', 4'-bridged nucleosides.2008

    • Author(s)
      Masayasu Kuwahara
    • Journal Title

      Nucleic Acids Res. 36

      Pages: 4257-4265

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biologically active 2-5A analogs containing 3' -0, 4' -C-propylene adenosine as potent RNase L agonists.2008

    • Author(s)
      Koji Morita
    • Journal Title

      Nucleic Acids Symp. Ser. 52

      Pages: 637-638

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Promotion of triplex formation by 2' -0, 4' -C-aminome-thylene bridged nucleic acid (2', 4' -BNA^NC)modification.2008

    • Author(s)
      Kiyomi Sasaki
    • Journal Title

      Nucleic Acids Symp. Ser. 52

      Pages: 419-420

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Synthesis and properties of 3′-amino-2′, 4′-BNA, a bridgednucleic acid with a N3'→P5' phosphoramidate linkage.2008

    • Author(s)
      Satoshi Obika
    • Journal Title

      Bioorg. Med. Chem. 16

      Pages: 9230-9237

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Total Synthesis of Leustroducsin B.2008

    • Author(s)
      Kazuyuki Miyashita
    • Journal Title

      J. Org. Chem. 73

      Pages: 5360-5370

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of anovel nucleoside analogue with S-type sugar conformation: 2'deoxy-trans-3', 4'-bridged nucleic acids2007

    • Author(s)
      尾崎朋久
    • Journal Title

      Tetrahedron 63

      Pages: 8977-8986

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] カルバマート骨格を有する新規架橋型人工核酸の合成とその評価2008

    • Author(s)
      西田勝、見玉」互也、馬場武、小比賀聡、今西武
    • Organizer
      第34回反応と合成の進歩シンポジウム
    • Place of Presentation
      京都
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 架橋型人工核酸BNA修飾によるsiRNAの高機能化2008

    • Author(s)
      佐藤寛之、津田直人、生川径祐、今西武、小比賀聡
    • Organizer
      第81回日本生化学会大会・第31回日本分子生物学会年会合同大会
    • Place of Presentation
      兵庫
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 2,2'一ビスベンズイミダゾール骨格を有した新規蛍光分子の開発とオリゴヌクレオチドラベル化に関する研究2008

    • Author(s)
      松山憲司、渡部徹也、兒玉哲也、小比賀聡、宮下和之、今西武
    • Organizer
      第三回バイオ関連化学合同シンポジウム2008
    • Place of Presentation
      神奈川
    • Related Report
      2008 Final Research Report
  • [Presentation] 3,4一エポキシピペリジン構造を有する新規DNAアルキル分子の合成と活性評価2008

    • Author(s)
      河田裕治、山口卓男、宮下和之、小比賀聡、今西武
    • Organizer
      第27回メディシナルケミストリーシンポジウム
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report
  • [Presentation] ウレア骨格を有する新規架橋型人工核酸の合成とその評価2008

    • Author(s)
      西田 勝
    • Organizer
      第18回アンチセンスシンポジウム
    • Place of Presentation
      岐阜
    • Related Report
      2008 Annual Research Report
  • [Presentation] 架橋型人工核酸BNAのsiRNAへの応用2008

    • Author(s)
      佐藤 寛之
    • Organizer
      第18回アンチセンスシンポジウム
    • Place of Presentation
      岐阜
    • Related Report
      2008 Annual Research Report
  • [Presentation] 架橋型人工核酸BNAのsiRNAへの展開2008

    • Author(s)
      佐藤寛之
    • Organizer
      第8回遺伝子デリバリー研究会
    • Place of Presentation
      兵庫
    • Related Report
      2008 Annual Research Report
  • [Presentation] 架橋型人工核酸BNAを用いたsiRNAによる遺伝子発現抑制2008

    • Author(s)
      佐藤寛之
    • Organizer
      第三回バイオ関連化学合同シンポジウム2008
    • Place of Presentation
      神奈川
    • Related Report
      2008 Annual Research Report
  • [Presentation] 2, 2'-ビスベンズイミダゾール骨格を有した新規蛍光分子の開発とオリゴヌクレオチドラベル化に関する研究2008

    • Author(s)
      松山 憲司
    • Organizer
      第三回バイオ関連化学合同シンポジウム2008
    • Place of Presentation
      神奈川
    • Related Report
      2008 Annual Research Report
  • [Presentation] クリックケミストリーを利用したオリゴヌクレオチド上での新規機能性核酸塩基の構築2008

    • Author(s)
      中原 基
    • Organizer
      第三回バイオ関連化学合同シンポジウム2008
    • Place of Presentation
      神奈川
    • Related Report
      2008 Annual Research Report
  • [Presentation] 3, 4-エポキシピペリジン構造を有するazinomycin類縁体の合成研究2008

    • Author(s)
      河田裕治
    • Organizer
      第38回複素環化学討論会
    • Place of Presentation
      広島
    • Related Report
      2008 Annual Research Report
  • [Presentation] 3, 4-エポキシピペリジン構造を有する新規DNAアルキル分子の合成と活性評価2008

    • Author(s)
      河田 裕治
    • Organizer
      第27回メディシナルケミストリーシンポジウム
    • Place of Presentation
      大阪
    • Related Report
      2008 Annual Research Report
  • [Presentation] 3, 4-エポキシピベリジン構造を有するazinomycin誘導体の合成研究2008

    • Author(s)
      河田 裕治
    • Organizer
      第94回有機合成シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report
  • [Presentation] 糖部をS型に束縛した架橋型人工核酸2'-deoxy型trans3', 4'-BNAの合成とその機能性評価2007

    • Author(s)
      菅谷建作
    • Organizer
      第27回有機合成若手セミナー
    • Place of Presentation
      京都大学薬学記念講堂
    • Year and Date
      2007-11-15
    • Related Report
      2007 Annual Research Report
  • [Presentation] 新規DNAアルキル化分子としての3, 4-エポキシピペリジン誘導体の合成2007

    • Author(s)
      河田裕治
    • Organizer
      第27回有機合成若手セミナー
    • Place of Presentation
      京都大学薬学記念講堂
    • Year and Date
      2007-11-15
    • Related Report
      2007 Annual Research Report
  • [Presentation] 糖部立体配座をS型に固定化した新規核酸類縁体(trans-3', 4'-BNA)の合成(3)2007

    • Author(s)
      菅谷建作
    • Organizer
      第57回日本薬学会近畿支部大会
    • Place of Presentation
      大阪薬科大学
    • Year and Date
      2007-10-27
    • Related Report
      2007 Annual Research Report
  • [Presentation] Synthesis andproperties of a 2'-deoxy analogue of trans-3',4'-BNA having an S-type sugar conformation2007

    • Author(s)
      兒玉哲也、松尾智恵子、小里英嗣、小比賀聡、宮下和之、今西武
    • Organizer
      5th International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      Tokyo
    • Related Report
      2008 Final Research Report
  • [Presentation] Studies toward the total synthesis of azinomycin A, a potent antitumor antibiotic2007

    • Author(s)
      山口卓男、河田裕治、宮下和之、今西武
    • Organizer
      The 21st International Congress for Heterocyclic Chemistry
    • Place of Presentation
      Sydney
    • Related Report
      2008 Final Research Report
  • [Presentation] Synthesis and properities of a 2'-deoxy analogue of trans-3', 4'-BNA having S-type sugar conformation2007

    • Author(s)
      菅谷建作
    • Organizer
      第5回国際核酸化学シンポジウム
    • Place of Presentation
      東京大学安田講堂
    • Related Report
      2007 Annual Research Report
  • [Presentation] Synthesis and chemical properties of a novel 2', 4'-bridged nucleic acid analogue bearing a seven-membered cyclic carbamate structure2007

    • Author(s)
      西田勝
    • Organizer
      第5回国際核酸化学シンポジウム
    • Place of Presentation
      東京大学安田講堂
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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