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Development of fluorescence probe for visualization of in-cell methylation events

Research Project

Project/Area Number 17K19492
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Pharmaceutical Sciences and related fields
Research InstitutionThe University of Tokushima

Principal Investigator

OTAKA Akira  徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (20201973)

Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords生体内メチル化 / 蛍光プローブ分子 / 生体反応可視化 / アデノシルホモシステイン / 蛍光プローブ / S-アデノシルホモシステイン / N-Sアシル転移
Outline of Final Research Achievements

Fluorescence-imaging of in-cell reactions using organic compounds has advanced physiological analyses of cell functions. Imaging of the methylation events involved in a wide variety of functional regulations of cell has remained to be achieved. Attempted researches allows for visualization of SAH hydrolase activity which is closely associated with the methylation events.

Academic Significance and Societal Importance of the Research Achievements

細胞内のメチル化反応は生体機能の恒常性維持に重要な働きをしており、メチル化の変調は各種疾患の発症に関与する。しかし、その重要性にも拘らず、メチル化現象を制御する酵素反応の可視化は達成されていない。そこで本研究はメチル化現象を細胞外から直接可視化するために必要とされる蛍光プローブ分子の開発を行うもので、細胞機能発現におけるメチル化の重要性解明に繋がり、その学術的意義は高い。さらに、将来的には各種疾患治療薬開発への道を拓くものであり、その社会的意義にも大きいなものがある。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (22 results)

All 2019 2018 2017

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (16 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] Direct Enantioselective Indolylation of Peptidyl Imine for the Synthesis of Indolyl Glycine-Containing Peptides2018

    • Author(s)
      Otaka Akira、Yamada Ken-ichi、Inokuma Tsubasa、Nishida Kodai
    • Journal Title

      HETEROCYCLES

      Volume: 97 Issue: 2 Pages: 1269-1269

    • DOI

      10.3987/com-18-s(t)86

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of Phosphatidylserine and Cholesterol on Membrane-mediated Fibril Formation by the N-terminal Amyloidogenic Fragment of Apolipoprotein A-I2018

    • Author(s)
      Mizuguchi Chiharu、Nakamura Mitsuki、Kurimitsu Naoko、Ohgita Takashi、Nishitsuji Kazuchika、Baba Teruhiko、Shigenaga Akira、Shimanouchi Toshinori、Okuhira Keiichiro、Otaka Akira、Saito Hiroyuki
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 5497-5497

    • DOI

      10.1038/s41598-018-23920-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Recyclable Hydrophobic Anchor-Tagged Asymmetric Amino Thiourea Catalyst2018

    • Author(s)
      Jichu Takahisa、Inokuma Tsubasa、Aihara Keisuke、Kohiki Taiki、Nishida Kodai、Shigenaga Akira、Yamada Ken-ichi、Otaka Akira
    • Journal Title

      ChemCatChem

      Volume: 10 Issue: 16 Pages: 3402-3405

    • DOI

      10.1002/cctc.201800714

    • NAID

      120006652009

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stapled BIG3 helical peptide ERAP potentiates antitumour activity for breast cancer therapeutics.2017

    • Author(s)
      Yoshimaru T, Aihara K, Komatsu M, Matsushita Y, Okazaki Y, Toyokuni S, Honda J, Sasa M, Miyoshi Y, Otaka A, Katagiri T
    • Journal Title

      Scientific Reports

      Volume: 印刷中 Issue: 1 Pages: 1821-1821

    • DOI

      10.1038/s41598-017-01951-6

    • NAID

      120006535017

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Elucidation of inhibitor-binding pocket of D-amino acid oxidase using docking simulation and N-sulfanylethylanilide-based labeling technology2017

    • Author(s)
      Kohiki, T.; Kato, Y.; Nishikawa, Y.;Yorita, K.; Sagawa, I.; Denda, M.; Inokuma, T.; Shigenaga, A.; Fukui, K.; Otaka, A.
    • Journal Title

      Organic & Biomolecular Chemistry

      Volume: 15 Issue: 25 Pages: 5289-5297

    • DOI

      10.1039/c7ob00633k

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemical Synthetic Platform for Chlorpromazine Oligomers That Were Reported as Photo-degradation Products of Chlorpromazine2017

    • Author(s)
      Kohiki Taiki、Nishikawa Yusuke、Inokuma Tsubasa、Shigenaga Akira、Otaka Akira
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 65 Issue: 12 Pages: 1161-1166

    • DOI

      10.1248/cpb.c17-00692

    • NAID

      130006235035

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Development of acyl transfer-based chemical biology tools for purification/selective labeling of target proteins.2019

    • Author(s)
      Shigenaga, A.; Morisaki, T.; Kohiki, T.; Denda, M.; Inokuma, T.; Otaka, A.
    • Organizer
      5th International Symposium for Medicinal Sciences
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 安定なイミンを用いたα-アミノリン酸の実用的不斉合成2018

    • Author(s)
      榊原 拓哉、猪熊 翼、重永 章、大髙 章、山田 健一
    • Organizer
      創薬懇話会 2018 in 志賀島
    • Related Report
      2018 Annual Research Report
  • [Presentation] トレーサブルリンカー を用いた共有結合性低分子の標的同定2018

    • Author(s)
      森崎 巧也、中山 淳、難波 康祐、重永 章、大髙 章
    • Organizer
      第50回若手ペプチド夏の勉強会
    • Related Report
      2018 Annual Research Report
  • [Presentation] がん抑制タンパク質PHB2からの創薬シード発掘2018

    • Author(s)
      安養寺 啓太央、粟飯原 圭祐、吉丸 哲郎、重永 章、片桐 豊雅、大髙 章
    • Organizer
      第50回若手ペプチド夏の勉強会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Novel methodology for the synthesis of-indolyl-glycine containing peptidevia direct asymmetric FriedelCrafts reactionto peptidyl imine.2018

    • Author(s)
      Inokuma, T.; Nishida, K.; Shigenaga, A.; Yamada, K.; Otaka, A.
    • Organizer
      35th European Peptide Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] S-アデノシルホモシステイン加水分解酵素の蛍光性基質の開発2018

    • Author(s)
      中西 雅之、古曳 泰規、重永 章、大髙 章、田中 信忠、北出 幸夫、日野 真美、野元 裕
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Combined approach of computation and enzymology to investigate novel D-amino acid oxidase inhibitors.2018

    • Author(s)
      Kato, Y.; Maita, N.; Kohiki, T.; Kurosawa, S.; Nishikawa, Y.; Sagawa, I.; Denda, M.; Inokuma, T.; Shishido, Y.; YORITA, K.; Shigenaga, A.; Otaka, A.; Fukui, K.
    • Organizer
      The 13th International Symposium of the Institute Network for Biomedical Sciences joint with the 3rd Symposium of the Inter-University Research Network for Trans-Omics Medicine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ペプチドイミンに対する不斉1,2-付加を基盤とする非天然アミノ酸含有ペプチドの不斉合成2018

    • Author(s)
      猪熊 翼、岡田 和貴、西田 航大、重永 章、大髙 章、山田 健一
    • Organizer
      第44回反応と合成の進歩シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 人工HDLの化学的性状と体内動態への影響に関する検討2018

    • Author(s)
      金山 忠史、奥平 桂一郎、大川内 健人、清水 太郎、重永 章、大髙 章、石田 竜弘
    • Organizer
      第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] SECmideを基盤としたターンオン型蛍光クリーバブルリンカーの開発2018

    • Author(s)
      森崎 巧也、重永 章、大髙 章
    • Organizer
      第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 非天然側鎖構造を有するα-アミノリン酸の実用的不斉合成2018

    • Author(s)
      榊原 拓哉、猪熊 翼、重永 章、大髙 章、山田 健一
    • Organizer
      第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development and application of novel protein labeling reagent SEAL.2018

    • Author(s)
      Kohiki, T.; Kato, Y.; Denda, M.; Nishikawa, Y.; YORITA, K.; Sagawa, I.; Inokuma, T.; Shigenaga, A.; Fukui, K.; Otaka, A.
    • Organizer
      10th International Peptide Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Screening of the effectors for human D-amino acid oxidase and the analyses of structure-activity relationships2017

    • Author(s)
      Kazuko YORITA, Sumire Kurosawa, Yuri Yoshida, Yoshiki Kashiwada, Shigeki Sano, Akira Otaka and Kiyoshi Fukui
    • Organizer
      The 19th triennial International Symposium on Flavins and Flavoproteins
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of anti-breast cancer stapled peptides targeting BIG3-PHB2 interaction2017

    • Author(s)
      Akira Otaka
    • Organizer
      AIMECS 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] N-Sアシル基転移を基盤としたタンパク質ラベル化法を用いたD-アミノ酸酸化酵素阻害剤の結合サイト解明研究2017

    • Author(s)
      古曳泰規、加藤有介、西川祐輔、頼田和子、佐川幾子、傳田将也、猪熊 翼、重永 章、福井 清、大髙 章
    • Organizer
      第56回日本薬学会・日本薬剤師会・日本大学病院薬剤師会中国四国支部学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] DAO分子表面に結合する阻害分子の計算科学的解析2017

    • Author(s)
      加藤有介、古曳泰規、西川祐輔、佐川幾子、傳田将也、猪熊 翼、宍戸裕二、重永 章、大髙 章、福井 清
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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