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Design of a novel affinity labeling probe exhibiting fluorescence and luminescence

Research Project

Project/Area Number 16K17930
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Bio-related chemistry
Research InstitutionOsaka University (2017)
The University of Tokyo (2016)

Principal Investigator

Yamaguchi Takao  大阪大学, 薬学研究科, 講師 (80596601)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsアフィニティーラベル化 / 標的タンパク質同定 / 発蛍光プローブ分子 / 創薬化学 / 生物活性化合物 / 標的タンパク質 / 標的同定 / アフィニティラベル化 / ケミカルバイオロジー / タンパク質化学修飾
Outline of Final Research Achievements

To elucidate the mechanism of bioactive small molecules, target protein identification methods are highly important. In this project, a novel affinity labeling probe having azidophthalimide structure was designed. By several model experiments, we revealed that the designed probe is suitable for selective fluorescent labeling of the target protein. Furthermore, the ligand-binding site was successfully determined by this method. We also successfully designed and synthesized several bioactive small molecules.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (19 results)

All 2018 2017 2016 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 1 results,  Acknowledgement Compliant: 4 results) Presentation (7 results) Remarks (1 results)

  • [Journal Article] Specific fluorescence labeling of target protein by using ligand-4-azidophthalimide conjugate2017

    • Author(s)
      Kosuke Chiba, Miwako Asanuma, Minoru Ishikawa, Yuichi Hashimoto, Kosuke Dodo, Mikiko Sodeoka, Takao Yamaguchi
    • Journal Title

      Chemical Communications

      Volume: 53 Issue: 62 Pages: 8751-8754

    • DOI

      10.1039/c7cc03252h

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Affinity Labeling with 4-Azidophthalimide (AzPI): Relation between Labeling Rate and Fluorescence Intensity2017

    • Author(s)
      Kosuke Chiba, Yuichi Hashimoto, Takao Yamaguchi
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 65 Issue: 10 Pages: 994-996

    • DOI

      10.1248/cpb.c17-00546

    • NAID

      130006109935

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Switching subtype-selectivity: Fragment replacement strategy affords novel class of peroxisome proliferator-activated receptor α/δ (PPARα/δ) dual agonists2017

    • Author(s)
      Ryuta Shioi, Shogo Okazaki, Tomomi Noguchi-Yachide, Minoru Ishikawa, Makoto Makishima, Yuichi Hashimoto, Takao Yamaguchi
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 27 Issue: 14 Pages: 3131-3134

    • DOI

      10.1016/j.bmcl.2017.05.037

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Photo-enhanced aqueous solubilization of an azo-compound2017

    • Author(s)
      Minoru Ishikawa, Takuya Ohzono, Takao Yamaguchi, Yasuo Norikane
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 6909-6909

    • DOI

      10.1038/s41598-017-06947-w

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis and evaluation of novel dual BRD4/HDAC inhibitors2017

    • Author(s)
      Amemiya Seika、Yamaguchi Takao、Hashimoto Yuichi、Noguchi-Yachide Tomomi
    • Journal Title

      Bioorganig and Medicinal Chemistry

      Volume: 25 Issue: 14 Pages: 3677-3684

    • DOI

      10.1016/j.bmc.2017.04.043

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of N6-(heteroarylcarbonyl)adenines as BRD4 inhibitors.2017

    • Author(s)
      Seika Amemiya、Takao Yamaguchi、Yuichi Hashimoto、 Tomomi Noguchi-Yachide
    • Journal Title

      Heterocycles

      Volume: 94 Issue: 6 Pages: 1107-1114

    • DOI

      10.3987/com-17-13667

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural Development Studies of Pyrazoloketone-Derived Acetyl-CoA Carboxylase Inhibitors2017

    • Author(s)
      Shogo Okazaki, Taki Sakai, Minoru Ishikawa, Yuichi Hashimoto, Takao Yamaguchi
    • Journal Title

      Heterocycles

      Volume: 95 Issue: 1 Pages: 595-607

    • DOI

      10.3987/com-16-s(s)30

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Dichloromaleimide (diCMI): A Small and Fluorogenic Reactive Group for Use in Affinity Labeling2016

    • Author(s)
      Kosuke Chiba, Yuichi Hashimoto, Takao Yamaguchi
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 64 Issue: 11 Pages: 1647-1653

    • DOI

      10.1248/cpb.c16-00501

    • NAID

      130005268074

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Discovery of N-(1-(3-(4-phenoxyphenyl)-1,2,4-oxadiazol-5-yl)ethyl)acetamides as novel acetyl-CoA carboxylase 2 (ACC2) inhibitors with peroxisome proliferator-activated receptor α/δ (PPARα/δ) dual agonistic activit2016

    • Author(s)
      Shogo Okazaki, Tomomi Noguchi-Yachide, Taki Sakai, Minoru Ishikawa, Makoto Makishima, Yuichi Hashimoto, Takao Yamaguchi
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 24 Issue: 21 Pages: 5258-5269

    • DOI

      10.1016/j.bmc.2016.08.045

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Structure-activity relationship studies of non-carboxylic acid peroxisome proliferator-activated receptorα/δ (PPARα/δ) dual agonists2016

    • Author(s)
      Shogo Okazaki, Ryuta Shioi, Tomomi Noguchi-Yachide, Minoru Ishikawa, Makoto Makishima, Yuichi Hashimoto, Takao Yamaguchi
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 24 Issue: 21 Pages: 5455-5461

    • DOI

      10.1016/j.bmc.2016.08.067

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Synthesis of scpBNA‐mC, -A, and -G Monomers and Evaluation of the Binding Affinities of scpBNA-Modified Oligonucleotides toward Complementary ssRNA and ssDNA2016

    • Author(s)
      Masahiko Horiba, Takao Yamaguchi, Satoshi Obika
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 81 Issue: 22 Pages: 11000-11008

    • DOI

      10.1021/acs.joc.6b02036

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] 各種置換基を導入したグアニジン架橋型人工核酸の合成2018

    • Author(s)
      堀江直宏、山口卓男、小比賀聡
    • Organizer
      日本化学会 第98春季年会(2018)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 5位に水酸基を有する2'-O-メチルシチジン誘導体の合成2018

    • Author(s)
      櫻井耀太、堀場昌彦、山口卓男、小比賀聡
    • Organizer
      日本薬学会 第138回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 標的タンパク質のリン酸化を選択的に誘導する分子の創製2017

    • Author(s)
      境太希、岡崎翔吾、石川稔、橋本祐一、山口卓男
    • Organizer
      日本薬学会 第137回年会
    • Place of Presentation
      東北大学、仙台国際センター、仙台市民会館(宮城県・仙台市)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] エステラーゼ活性評価のための蛍光turn-ON型プローブ分子の創製2017

    • Author(s)
      岡田佳那、山口卓男、どど孝介、袖岡幹子、小比賀聡
    • Organizer
      第67回日本薬学会近畿支部総会・大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] アジドフタルイミドを用いた発蛍光型光アフィニティーラベル化法の開発2016

    • Author(s)
      千葉幸介、橋本祐一、山口卓男
    • Organizer
      日本ケミカルバイオロジー学会 第11回年会
    • Place of Presentation
      京都テルサ(京都府・京都市)
    • Year and Date
      2016-06-15
    • Related Report
      2016 Research-status Report
  • [Presentation] PPARα/δデュアル転写誘導活性を有する新規ACC2阻害剤の創出2016

    • Author(s)
      山口卓男、岡崎翔吾、境太希、谷内出友美、石川稔、橋本祐一
    • Organizer
      日本ケミカルバイオロジー学会 第11回年会
    • Place of Presentation
      京都テルサ(京都府・京都市)
    • Year and Date
      2016-06-15
    • Related Report
      2016 Research-status Report
  • [Presentation] アジドフタルイミドを用いる新規標的タンパク質同定法の創出2016

    • Author(s)
      千葉幸介、橋本祐一、山口卓男
    • Organizer
      第60回日本薬学会関東支部大会
    • Place of Presentation
      東京大学大学院薬学研究科(東京都・文京区)
    • Related Report
      2016 Research-status Report
  • [Remarks] 東京大学 分子細胞生物学研究所 生体有機化学研究分野

    • URL

      http://www.iam.u-tokyo.ac.jp/chem/IMCB-8ken-HP/Index.html

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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