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Design and synthesis of chiral peptide nucleic acid for antigene therapeutics

Research Project

Project/Area Number 24590135
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Drug development chemistry
Research InstitutionTeikyo University (2015)
The University of Tokyo (2012-2014)

Principal Investigator

SUGIYAMA TORU  帝京大学, 薬学部, 准教授 (40242036)

Co-Investigator(Kenkyū-buntansha) KITTAKA ATSUSHI  帝京大学, 薬学部, 教授 (00214833)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords核酸 / ゲノム / 遺伝子 / 癌 / 有機化学 / ペプチド核酸
Outline of Final Research Achievements

The synthesis of new β-Lys PNA monomers and their incorporation into a 10-residue PNA sequence have been achieved. PNA containing β-Lys PNA units formed a stable hybrid duplex with DNA. However, incorporation of β-Lys PNA units caused destabilization of PNA-DNA duplexes to some extent. Electrostatic attractions between β-PNA and DNA could reduce this destabilization effect. Subsequently, bipyridine-conjugated β-Lys PNA was prepared and exhibited sequence selective cleavage of DNA. Based on the structures of the cleavage products and molecular modeling, we reasoned that bipyridine moiety locates within the minor groove of the PNA-DNA duplexes. The lysine side chain of β-PNA is a versatile handle for attaching various functional molecules.

Report

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

    (18 results)

All 2016 2015 2014 2013 2012

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (12 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Synthesis of PNA oligomers containing modified deazaguanines for the development of functional PNA2016

    • Author(s)
      Toru Sugiyama, Keiko Kuwata, Yasutada Imamura, Yosuke Demizu, Masaaki Kurihara, Masashi Takano, Atsushi Kittaka
    • Journal Title

      Peptide Science

      Volume: 2015 Pages: 307-308

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peptide Nucleic Acid with a Lysine side chain at the β-Position: Synthesis and Application for DNA Cleavage2016

    • Author(s)
      Toru Sugiyama, Keiko Kuwata, Yasutada Imamura, Yosuke Demizu, Masaaki Kurihara, Masashi Takano, Atsushi Kittaka
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 64

    • NAID

      130005160035

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Modified deazaguanines for the synthesis of PNA2015

    • Author(s)
      Toru Sugiyama, Keiko Kuwata, Yasutada Imamura, Yosuke Demizu, Masaaki Kurihara, Masashi Takano, Atsushi Kittaka
    • Journal Title

      Peptide Science

      Volume: 2014 Pages: 87-88

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Peptide Nucleic Acid to Reduce Type I Collagen Production by Fibroblast Cells2015

    • Author(s)
      Yasutada Imamura, Suzuka Tsuboi, Toru Sugiyama, Atsushi Kittaka, and Yonchol Shin
    • Journal Title

      Open Journal of Medicinal Chemistry 2015

      Volume: 5 Issue: 01 Pages: 1-8

    • DOI

      10.4236/ojmc.2015.51001

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sequence-specific cleavage of DNA by β-peptide nucleic acid bearing a pendant metal complex2014

    • Author(s)
      Toru Sugiyama, keiko Kuwata, Yasutada Imamura, Yosuke Demizu, Masaaki Kurihara, Masashi Takano, Atsushi Kittaka
    • Journal Title

      Peptide Science

      Volume: 2013 Pages: 369-370

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis of β-chiral peptide nucleic acids bearing lysine side chains2013

    • Author(s)
      Toru Sugiyama
    • Journal Title

      Peptide Science

      Volume: 2012 Pages: 385-386

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] デアザグアニン誘導体を持つPNAの合成2016

    • Author(s)
      杉山 亨、桑田啓子、今村保忠、出水庸介、栗原正明、高野真史、橘高敦史
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 25-ヒドロキシビタミンD3ラクトン代謝産物と異性体の合成研究2016

    • Author(s)
      樋口恵理香、杉山 亨、高野真史、上杉志成、橘高敦史
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 22-ヒドロキシ-2-メチリデン-19, 23, 24, 25, 26, 27-へキサノルビタミンD3と異性体の合成2016

    • Author(s)
      川越文裕、高野真史、松本洋太郎、杉山 亨、上杉志成、橘高敦史
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 修飾デアザグアニン含有PNAオリゴマーの合成2015

    • Author(s)
      杉山 亨、桑田啓子、今村保忠、出水庸介、栗原正明、高野真史、橘高敦史
    • Organizer
      第33回メディシナルケミストリーシンポジウム
    • Place of Presentation
      幕張国際研修センター(千葉県千葉市)
    • Year and Date
      2015-11-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] 機能性PNAの開発を目指した修飾デアザグアニン含有PNAオリゴマーの合成2015

    • Author(s)
      杉山 亨、桑田啓子、今村保忠、出水庸介、栗原正明、高野真史、橘高敦史
    • Organizer
      第52回ペプチド討論会
    • Place of Presentation
      平塚市中央公民館(神奈川県平塚市)
    • Year and Date
      2015-11-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] Incorporation of a peptide nucleic acid into a normal human fibroblast cell reduced type I collagen production2015

    • Author(s)
      Yasutada Imamura, Suzuka Tsuboi, Toru Sugiyama, Atsushi Kittaka, Yonchol Shin
    • Organizer
      9th International Conference on Proteoglycans and 10th Pan Pacific Connective Tissue Societies Symposium
    • Place of Presentation
      Ewha Womans University(韓国ソウル)
    • Year and Date
      2015-08-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] デアザグアニン誘導体を持つPNAモノマーの合成2015

    • Author(s)
      杉山 亨、桑田啓子、今村保忠、出水庸介、栗原正明、高野真史、橘高敦史
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸学院大学(兵庫県神戸市)
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] PNA合成のための修飾デアザグアニン2014

    • Author(s)
      杉山 亨、桑田啓子、今村保忠、出水庸介、栗原正明、高野真史、橘高敦史
    • Organizer
      第51回ペプチド討論会
    • Place of Presentation
      徳島大学蔵本キャンパス大塚講堂(徳島県徳島市)
    • Year and Date
      2014-10-22 – 2014-10-24
    • Related Report
      2014 Research-status Report
  • [Presentation] 側鎖に金属錯体を持ったβ-PNAによる配列特異的DNA切断2014

    • Author(s)
      杉山 亨、桑田啓子、今村保忠、出水庸介、栗原正明、高野真史、橘高敦史
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本市総合体育館 (熊本県熊本市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Sequence-specific cleavage of DNA by β-peptide nucleic acid bearing a pendant metal complex2013

    • Author(s)
      Toru Sugiyama, keiko Kuwata, Yasutada Imamura, Yosuke Demizu, Masaaki Kurihara, Masashi Takano, Atsushi Kittaka
    • Organizer
      4th Asia-Pacific International Peptide Symposium
    • Place of Presentation
      ホテル阪急エキスポパーク(大阪府吹田市)
    • Related Report
      2013 Research-status Report
  • [Presentation] β-リジンPNAの合成2013

    • Author(s)
      杉山 亨
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      パシフィコ横浜 ( 神奈川県 横浜市)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] リジン側鎖を持ったβ―キラルペプチド核酸の合成2012

    • Author(s)
      杉山 亨
    • Organizer
      第49回ペプチド討論会
    • Place of Presentation
      かごしま県民交流センター ( 鹿児島県 鹿児島市)
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2013-05-31   Modified: 2019-07-29  

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