• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Exploration of Innovative Methods for the synthesis of RNA Capable of Machting Requirement for New day

Research Project

Project/Area Number 21241053
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Living organism molecular science
Research InstitutionTokyo Institute of Technology

Principal Investigator

SEKINE Mitsuo  東京工業大学, 大学院・生命理工学研究科, 教授 (40111679)

Co-Investigator(Kenkyū-buntansha) OHKUBO Akihiro  東京工業大学, 大学院・生命理工学研究科, 助教 (60376960)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥25,480,000 (Direct Cost: ¥19,600,000、Indirect Cost: ¥5,880,000)
Fiscal Year 2011: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Fiscal Year 2010: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Keywords生体高分子 / RNA合成 / 筋ジストロフィー / 2'水酸基の保護基 / RNA医薬 / Michael反応 / シアノエチル基 / アミダイトユニット / MCE基 / 固相合成法 / 2'水酸某の保護基 / 塩基部無保護 / RNAの化学合成 / マイケル反応 / 2'-保護基 / シアノエチル化 / 脱アミノ化反応 / 合成モノマーユニット / アデノシン / グアノシン
Research Abstract

An innovative method for the highly 2'-O-selective modification of ribonucleoside derivatives with cyanoethyl and 2-(N-methylcarbamoyl) ethyl(MCE) groups by Michael reaction has been developed. Various 2'-O-modified RNA derivatives were synthesized by using this new method. Extensive studies using these synthetic RNA derivatives showed they had more effective exon-skipping activities that indicate the efficacy as drugs for Duchenne muscular dystrophy.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (51 results)

All 2012 2011 2010 2009 Other

All Journal Article (26 results) (of which Peer Reviewed: 26 results) Presentation (24 results) Remarks (1 results)

  • [Journal Article] Synthesis and Properties of Cationic 2'-O-[ N-(4-aminobutyl) carbamoyl] modified Oligonucleotides.2012

    • Author(s)
      K. Seio, M. Tokugawa, T. Kanamori, H. Tsunoda, A. Ohkubo, and M. Sekine
    • Journal Title

      Bioorg. Med. Chem. Lett

      Volume: 22巻 Pages: 2470-2473

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA Duplexes and Triplex-Forming Oligodeoxynucleotides Incorporating Modified Nucleosides Forming Stable and Selective Triplexes2012

    • Author(s)
      T. Kanamori, Y. Masaki, M. Mizuta, H. Tsunoda, A. Ohkubo, M. Sekine, and K. Seio
    • Journal Title

      Org. Biomol. Chem

      Volume: 10巻 Pages: 1007-1013

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Formation of New Base Pairs between Inosine and 5-Methyl-2-thiocytidine Derivatives2012

    • Author(s)
      A. Ohkubo, Y. Nishino, Y. Ito, H. Tsunoda, K. Seio, and M. Sekine
    • Journal Title

      Org. Biomol. Chem

      Volume: 10巻 Pages: 10-13

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesi and Properties of Cationic 2'-O-[N-(4-aminobutyl)carbamoyl]modified Oligonucleotides2012

    • Author(s)
      Seio, K.; Tokugawa, M.; Kanamori, T.; Tsunoda, H.; Ohkubo, A.; Sekine, M
    • Journal Title

      Bioorg.Med.Chem.Lett

      Volume: 22 Pages: 2470-2473

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA Duplexes and Triplex-Forming Oligodeoxynucleotides Incorporating Modified Nucleosides Forming stable and Selective Triplexes2012

    • Author(s)
      Kanamori, T.; Masaki, Y.; Mizuta, M.; Tsunoda, H.; Ohkubo, A.; Sekine, M.; Seio, K.
    • Journal Title

      Org.Biomol.Chem

      Volume: 10 Issue: 5 Pages: 1007-1013

    • DOI

      10.1039/c1ob06411h

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Formation of New Base Pairs between Inosine and 5-Methyl-2-thiocytidine Derivatives2012

    • Author(s)
      Ohkubo, A.; Nishino, Y.; Ito, Y.; Tsunoda, H.; Seio, K.; Sekine
    • Journal Title

      Org.Biomol.Chem.

      Volume: 10 Issue: 10 Pages: 2008-2010

    • DOI

      10.1039/c2ob06641f

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of 2'-O-[ 2-(N-Methylcarbamoyl) ethyl] ribonucl eosides Using Oxa-Michael Reaction and Chemical and Biological Properties of Oligonucleotide Derivatives Incorporating These Modified Ribonucleosides2011

    • Author(s)
      T. Yamada, N. Okaniwa, H. Saneyoshi, A. Ohkubo, K. Seio, T. Nagata, Y. Aoki, S. Takeda, and M. Sekine
    • Journal Title

      J. Org. Chem

      Volume: 76巻 Pages: 3042-3053

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and Hybridization Properties of 2'-O-Methylated Oligoribonucleotides Incorporating 2'-O-Naphthyluridines2011

    • Author(s)
      M. Sekine, Y. Oeda, Y. Iijima, H. Taguchi, A. Ohkubo, and K. Seio
    • Journal Title

      Org. Biomol. Chem

      Volume: 9巻 Pages: 210-218

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and Hybridization Properties of 2'-0-Methylated Oligoribonucleotides Incorporating 2'-0-Naphthyluridines2011

    • Author(s)
      M.Sekine, et al.
    • Journal Title

      Org.Biomol.Chem.

      Volume: 76 Pages: 210-218

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of 2'-0-[2-(N-Methylcarbamoyl) ethyl] riboncleosides Using Oxa-Michael Reaction and Chemical and Biological Properties of Oligonucleotide Derivatives Incorporating These Modified Ribonucleosides2011

    • Author(s)
      T.Yamada, et al.
    • Journal Title

      J.Org.Chem.

      Volume: 9(in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Linear Relationship between Deformability and Thermal Stability of 2'-O-Modified RNA Hetero Duplexes2010

    • Author(s)
      Y. Masaki, R. Miyasaka, A. Ohkubo, K. Seio, and M. Sekine
    • Journal Title

      J. Phys. Chem.(B)

      Volume: 114巻 Pages: 2517-2524

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of 6-N-(Benzothiazol-2-yl) deoxyadenosine and Its Exciton-coupled Circular Dichroism2010

    • Author(s)
      Y. Masaki, A. Ohkubo, K. Seio, and M. Sekine
    • Journal Title

      Bioorg. Med. Chem

      Volume: 18巻 Pages: 567-572

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of 6-N-(benzothiazol-2-yl) deoxyadenosine and its exciton-coupled circular dichroism2010

    • Author(s)
      Y.Masaki, et al.
    • Journal Title

      J.Phys.Chem.(B)

      Volume: 114 Pages: 2517-2524

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Linear Relationship between Deformability and Thermal Stability of 2'-O-Modified RNA Hetero Duplexes2010

    • Author(s)
      Y.Masaki, R.Miyasaka, A.Ohkubo, K.Seio, M.Sekine
    • Journal Title

      J.Phys.Chem.(B) 114

      Pages: 2517-2524

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] icrowave-Assisted Synthesis of 2'-O-Aryluridine Derivatives2009

    • Author(s)
      Y. Oeda, Y. Iijima, H. Taguchi, A. Ohkubo, K. Seio, and M. Sekine
    • Journal Title

      Org. Lett

      Volume: 11巻 Pages: 5582-5585

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and hybridization of 2'-O-methyl-RNAs incorporating 2'-O-carbamoyluridine and unique participation of the carbamoyl group in U. G base pair2009

    • Author(s)
      K. Seio, R. Tawarada, T. Sasami, M. Serizawa, M. Ise, A. Ohkubo, and M. Sekine
    • Journal Title

      Bioorg. Med. Chem

      Volume: 17巻 Pages: 7275-7280

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Efficient solid-phase synthesis of oligodeoxynucleotides having a 5'-terminal 2, 2, 7-trimethylguanosine pyrophosphate linkage2009

    • Author(s)
      A. Ohkubo, K. Sasaki, Y. Noma, H. Tsunoda, K. Seio, and M. Sekine
    • Journal Title

      Bioorg. Med. Chem

      Volume: 17巻 Pages: 4819-4824

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and Properties of Nucleoside Derivatives Masked by the Chemically Stable 2-(Trimethylsilyl) benzoyl Group2009

    • Author(s)
      K. Yamada, H. Taguchi, A. Ohkubo, K. Seio, and M. Sekine
    • Journal Title

      Bioorg. Med. Chem

      Volume: 17巻 Pages: 5928-5932

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of terminally modifiedoligonucleotides and their hybridization dependence on the size of the target RNAs2009

    • Author(s)
      K. Seio, Y. Takaku, K. Miyazaki, Y. Masaki, A. Ohkubo, and M. Sekine
    • Journal Title

      Org. Biomol. Chem

      Volume: 7巻 Pages: 2440-2451

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] 3'-Terminal Nucleosides Having a SilylLinker into Polymer Supports without Base Protection2009

    • Author(s)
      A. Ohkubo, Y. Noma, K. Aoki, H. Tsunoda, K. Seio and M. Sekine
    • Journal Title

      J. Org. Chem

      Volume: 74巻 Pages: 2817-2823

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Introduction of 3'-Terminal Nucleosides Having a Silyl Linker into Polymer Supports without Base Protection2009

    • Author(s)
      A.Ohkubo, Y.Noma, K.Aoki, H.Tsunoda, K.Seio, M Sekine
    • Journal Title

      J.Org.Chem. 74

      Pages: 2817-2823

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of terminally modified oligonucleotides and their hybridization dependence on the size of the target RNAs2009

    • Author(s)
      K.Seio, Y.Takaku, K.Miyazaki, Y.Masaki, A.Ohkubo, M.Sekine
    • Journal Title

      Org.Biomol.Chem. 7

      Pages: 2440-2451

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient solid-phase synthesis of oligodeoxynucleotides having a 5'-terminal 2, 2, 7-trimethylguanosine pyrophosphate linkage2009

    • Author(s)
      A.Ohkubo, K.Sasaki, Y.Noma, H.Tsunoda, K.Seio, M.Sekine
    • Journal Title

      Bioorg.Med.Chem. 17

      Pages: 4819-4824

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and Properties of Nucleoside Derivatives Masked by the Chemically Stable 2-(Trimethylsilyl) benzoyl Group2009

    • Author(s)
      K.Yamada, H.Taguchi, A.Ohkubo, K.Seio, M.Sekine
    • Journal Title

      Bioorg.Med.Chem. 17

      Pages: 5928-5932

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and hybridization of 2'-O-methyl-RNAs incorporating 2'-O-carbamoyluridine and unique participation of the carbamoyl group in U-G base pair2009

    • Author(s)
      K.Seio, R.Tawarada, T.Sasami, M.Serizawa, M.Ise, A.Ohkubo, M.Sekine
    • Journal Title

      Bioorg.Med.Chem. 17

      Pages: 7275-7280

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Microwave-Assisted Synthesis of 2'-O-Aryluridine Derivatives2009

    • Author(s)
      Y.Oeda, Y.Iijima, H.Taguchi, A.Ohkubo, K.Seio, M.Sekine
    • Journal Title

      Org.Lett. 11

      Pages: 5582-5585

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 6-チオプリンおよび4-チオピリミジン誘導体を含むオリゴヌクレオチドの合成とその三重鎖形成能2012

    • Author(s)
      服部勇作・印出健志・山田健司・伊藤優・角田浩佑・大窪章寛・清尾康志・関根光雄
    • Organizer
      第92春季年会
    • Place of Presentation
      慶應大学
    • Year and Date
      2012-03-25
    • Related Report
      2011 Final Research Report
  • [Presentation] DNA二重鎖および三重鎖に導入したデオキシシュードイソシチジンの塩基対形成能の評価2012

    • Author(s)
      金森功吏・山口慧・角田浩佑・大窪章寛・関根光雄・清尾康志
    • Organizer
      第92春季年会
    • Place of Presentation
      慶應大学
    • Year and Date
      2012-03-25
    • Related Report
      2011 Final Research Report
  • [Presentation] 4-O-(アミノエチル)ウリジン誘導体を含む新規三重鎖形成核酸の合成とその性質2012

    • Author(s)
      伊藤優・山田健司・角田浩佑・大窪章寛・清尾康志・関根光雄
    • Organizer
      第92春季年会
    • Place of Presentation
      慶應大学
    • Year and Date
      2012-03-25
    • Related Report
      2011 Final Research Report
  • [Presentation] 4-O-(アミノエチル)ウリジン誘導体を含む新規三重鎖形成核酸の合成とその性質2012

    • Author(s)
      伊藤優, et al.
    • Organizer
      第92春季年会プログラム
    • Place of Presentation
      慶應大学
    • Year and Date
      2012-03-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] DNA二重鎖および三重鎖に導入したデオキシシュードイソシチジンの塩基対形成能の評価2012

    • Author(s)
      山口慧, et al.
    • Organizer
      第92春季年会プログラム
    • Place of Presentation
      慶應大学
    • Year and Date
      2012-03-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] 6-チオプリンおよび4-チオピリミジン誘導体を含むオリゴヌクレオチドの合成とその三重鎖形成能2012

    • Author(s)
      印出健志, et al.
    • Organizer
      第92春季年会プログラム
    • Place of Presentation
      慶應大学
    • Year and Date
      2012-03-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] TMGキャップアナロクを有するモルフォリノ核酸の合成2011

    • Author(s)
      山田研・横内瑛・鈴木真・角田浩佑・大窪章寛・清尾康志・関根光雄
    • Organizer
      第21回アンチセンスシンポジウムおよび第11回遺伝子・デリバリー研究会シンポジウム
    • Place of Presentation
      大阪大学コンベンションセンター
    • Year and Date
      2011-09-01
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 新規人工核酸の創成研究2011

    • Author(s)
      関根光雄
    • Organizer
      日本化学会関東支部主催群馬地区講演会
    • Place of Presentation
      群馬大学
    • Year and Date
      2011-07-08
    • Related Report
      2011 Final Research Report
  • [Presentation] 新規人工核酸の創成研究2011

    • Author(s)
      関根光雄
    • Organizer
      日本化学会関東支部主催群馬地区講演会
    • Place of Presentation
      群馬大学(招待講演)
    • Year and Date
      2011-07-08
    • Related Report
      2011 Annual Research Report
  • [Presentation] Synthesis and Biological Properties of Synthesis and Biological Properties of 2'-O-Modified Oligoribonucleotide Derivatives2011

    • Author(s)
      M. Sekine
    • Organizer
      XVth Symposium on Chemistry of Nucleic Acid Components SCNAC 2011
    • Place of Presentation
      Cechy, eska republika
    • Year and Date
      2011-06-09
    • Related Report
      2011 Final Research Report
  • [Presentation] Synthesis and Biological Properties of Synthesis and Biological Properties of 2'-O-Modified Oligoribonucleotide Derivatives2011

    • Author(s)
      Sekine, M.
    • Organizer
      XVth Symposium on Chemistry of Nucleic Acid Components SCNAC 2011
    • Place of Presentation
      Cechy, Ceska republika(招待講演)
    • Year and Date
      2011-06-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] Synthesis and Properties of Modified Oligonucleotides Capable Triplex Formation with DNA Duplexes under Neutral Conditions2010

    • Author(s)
      M. Sekine
    • Organizer
      2010環太平洋国際化学会議
    • Place of Presentation
      Hawaii, Convention Center, USA
    • Year and Date
      2010-12-15
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 2'-O-MCEオリゴヌクレオチドの合成と性質2010

    • Author(s)
      山田剛史、岡庭夏己、武田伸一、永田哲也、實吉尚郎、大窪章寛、関根光雄
    • Organizer
      第20回アンチセンスシンポジウム
    • Place of Presentation
      甲南大学
    • Year and Date
      2010-12-02
    • Related Report
      2011 Final Research Report
  • [Presentation] 2'-0-MCEオリゴヌクレオチドの合成と性質2010

    • Author(s)
      山田剛史, et al.
    • Organizer
      第20回アンチセンスシンポジウム
    • Place of Presentation
      甲南大学ポートアイランドキャンパス
    • Year and Date
      2010-12-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] Synergetic effects of 2-thiolation and 5-propynylation of the uracil base on the stability of RNA duplexes2010

    • Author(s)
      R. Miyasaka, Y. Masaki, H. Tsunoda, A. Ohkubo, K. Seio, and M. Sekine
    • Organizer
      第37回国際核酸化学シンポジウム
    • Place of Presentation
      よこはま・はまぎんホール
    • Year and Date
      2010-11-10
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Synthesis and Properties of 2'-O-[ 2-(N-methyl) carbamoyl] ethyl-RNAs2010

    • Author(s)
      T. Yamada, N. Okaniwa, H. Saneyoshi, A. Ohkubo, K. Seio, T. Nagata, S. Takeda, and M. Sekine
    • Organizer
      第37回国際核酸化学シンポジウム
    • Place of Presentation
      よこはま・はまぎんホール
    • Year and Date
      2010-11-10
    • Related Report
      2011 Final Research Report
  • [Presentation] Synthesis and Properties of 2'-0-[2-(N-methyl) carbamoyl] ethyl-RNAs2010

    • Author(s)
      T.Yamada, et al.
    • Organizer
      第37回国際核酸化学シンポジウム
    • Place of Presentation
      よこはま・はまぎんホール
    • Year and Date
      2010-11-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] 新規核酸医薬の創成を指向した合成研究2010

    • Author(s)
      関根光雄
    • Organizer
      第54回日本薬学会関東支部大会
    • Place of Presentation
      東京薬科大学
    • Year and Date
      2010-10-02
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Relationship Between Thermal Stability and Deformability of Modified RNA, XIX International Round Table on Nucleosides2010

    • Author(s)
      正木慶昭・宮坂隆太・角田浩佑・大窪章寛・清尾康志・関根光雄
    • Organizer
      Nucleotides and Nucleic Acids
    • Place of Presentation
      クロードベルナールリヨン第一大学
    • Year and Date
      2010-09-01
    • Related Report
      2011 Final Research Report
  • [Presentation] RELATIONSHIP BETWEEN THERMAL STABILITY AND DEFORMABILITY OF MODIFIED RNA2010

    • Author(s)
      正木慶昭, et al.
    • Organizer
      XIX International round Table on Nucleosides, Nucleotides and Nucleic Acids
    • Place of Presentation
      クロードベルナールリヨン第一大学
    • Year and Date
      2010-09-01
    • Related Report
      2010 Annual Research Report
  • [Presentation] 2'水酸基修飾アンチセンスオリコヌクレオチトの合成と筋シストロフィーを対象としたエキソンスキッヒンク評価2010

    • Author(s)
      岡庭夏己, et al.
    • Organizer
      第12回日本RNA学会年会
    • Place of Presentation
      一橋記念講堂:学術総合センター
    • Year and Date
      2010-07-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] New Triplex Forming Oligonucleotides Capable of Binding to DNA Duplexes under Neutral Conditions2010

    • Author(s)
      M. Sekine
    • Organizer
      Heidelberg University-Tokyo Institute of Technology Joint Symposium on
    • Place of Presentation
      Wroclaw University, Poland
    • Year and Date
      2010-07-16
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Triplex Forming ligonucleotides Containing Thiolated Nucleobases2010

    • Author(s)
      M. Sekine
    • Organizer
      ICPC2010-Symposium on Biophosphates
    • Place of Presentation
      Wroclaw University, Poland
    • Year and Date
      2010-07-16
    • Related Report
      2011 Final Research Report
  • [Presentation] Triplex Forming Oligonucleotides Containing Thiolated Nucleobases2010

    • Author(s)
      M.Sekine
    • Organizer
      ICPC2010-Symposium on Biophosphates
    • Place of Presentation
      Wroclaw University, Poland
    • Year and Date
      2010-07-13
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.skn.bio.titech.ac.jp/Home.ht

    • Related Report
      2011 Final Research Report

URL: 

Published: 2010-08-23   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi