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

脂質関連内因性分子の新機能発掘と調節

Publicly Offered Research

Project AreaChemical Biology using bioactive natural products as specific ligands: identification of molecular targets and regulation of bioactivity
Project/Area Number 26102728
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Science and Engineering
Research InstitutionKyoto University

Principal Investigator

上杉 志成  京都大学, 物質-細胞統合システム拠点, 教授 (10402926)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsケミカルバイオロジー
Outline of Annual Research Achievements

本研究の目的は、脂質関連内因性分子の新機能を発掘し、分子標的を同定し、その新機能を人工的に調節することである。脂質関連内因性分子という天然物を出発点として、標的タンパク質の生物機能を理解し、最後に合成化学によって内因性分子を模倣する人工分子を創製する。つまり、「ケムーバイオーケム」の研究展開を脂質関連内因性分子で実践する。平成27年度では以下の成果をあげた。
(1)具体的な脂質内因性分子研究の例として、独自先行研究をすすめた。スクリーニングにより、ビタミンD誘導体の新しい機能を発見した。平成27年度はケミカルバイオロジー技術と細胞生物学を融合することで、25ヒドロキシビタミンD3の直接の標的の一つがSCAPであることがわかった。この相互作用によって、SCAPがユビキチン化されて、プロテアゾーム分解される。SCAPが分解されると、続いてSREBPを分解することがわかった。これらの成果をまとめ、現在論文投稿中である。
(2)水酸化ビタミンD3のSREBP阻害機能のみを選択的に模倣する合成化合物のプロトタイプを得た。誘導体展開を行い、優れた化合物を得た。これらの人工ビタミンDはPCT出願し(PCT/JP2015/006462)、米国のベンチャー企業へ導出した。
(3)領域研究協力者の理研吉田主任研究員に脂質関連内因性分子ライブラリー(約300化合物)を配布し、アシルドーパミンがHIF-1αを活性化することを発見した。詳細な解析の結果、アシルドーパミンの標的を決定した。
(4)領域内の三尾らのグループと、ワサビ成分の受容体であるTRPA1受容体について共同研究を続行した。この共同研究の成果をJACS誌に報告した。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (52 results)

All 2016 2015 2014 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 2 results,  Open Access: 2 results) Presentation (41 results) (of which Int'l Joint Research: 12 results,  Invited: 39 results) Book (1 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] A potent and site-selective agonist of TRPA1.2015

    • Author(s)
      Takaya, J., Mio, K., Shiraishi, T., Kurokawa, T., Otsuka, S., Mori, Y., Uesugi, M.
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 137 Issue: 50 Pages: 15859-15864

    • DOI

      10.1021/jacs.5b10162

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Intracellular generation of a diterpene-peptide conjugate that inhibits 14-3-3-mediated interactions.2015

    • Author(s)
      Parvatkar P., Kato N., Uesugi M., Sato S., Ohkanda J.
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 137 Issue: 50 Pages: 15624-15627

    • DOI

      10.1021/jacs.5b09817

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Live-cell Imaging of Endogenous mRNAs with a Small Molecule2015

    • Author(s)
      Sato, S.*, Watanabe, M., Katsuda, Y., Murata, A., Wang, D. O., Uesugi M.
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 54 Issue: 6 Pages: 1855-1858

    • DOI

      10.1002/anie.201410339

    • NAID

      120005619801

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A chemical probe that labels human pluripotent stem cells2014

    • Author(s)
      Hirata N, Nakagawa M, Fujibayashi Y, Yamauchi K, Murata A, Minami I, Tomioka M, Kondo T, Kuo TF, Endo H, Inoue H, Sato S, Ando S, Kawazoe Y, Aiba K, Nagata K, Kawase E, Chang YT, Suemori H, Eto K, Nakauchi H, Yamanaka S, Nakatsuji N, Ueda K, Uesugi M
    • Journal Title

      Cell reports

      Volume: 6 Issue: 6 Pages: 1165-74

    • DOI

      10.1016/j.celrep.2014.02.006

    • NAID

      120005466668

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Selective elimination of human pluripotent stem cells by a marine natural product derivative.2014

    • Author(s)
      Ting-Fang Kuo, Di Mao, Nao Hirata, Bilon Khambu, Yasuhisa Kimura, Eihachiro Kawase, Hiroki Shimogawa, Makoto Ojika, Norio Nakatsuji, Kazumitsu Ueda, and Motonari Uesugi
    • Journal Title

      J Am Chem Soc

      Volume: 136 Issue: 28 Pages: 9798-9801

    • DOI

      10.1021/ja501795c

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Synthetic Molecules That Protect Cells from Anoikis and Their Use in Cell Transplantation2014

    • Author(s)
      Frisco-Cabanos, H.L., Watanabe, M., Okumura, N., Kusamori, K., Takemoto, N., Takaya, J., Sato, S., Yamazoe, S., Takakura, Y., Kinoshita, S., Nishikawa, M., Koizumi, M., Uesugi, M
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 53 Issue: 42 Pages: 11208-11213

    • DOI

      10.1002/anie.201405829

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Affinity-Based Isolation of Molecular Targets of Clinically Used Drugs2014

    • Author(s)
      Sato, S., Uesugi, M.
    • Journal Title

      Concepts and Case Studies in Chemical Biology

      Volume: 15 Pages: 221-230

    • DOI

      10.1002/9783527687503.ch15

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] Synthetic Molecules for Cell Therapy2016

    • Author(s)
      Uesugi, M.
    • Organizer
      2016 Queenstown Molecular Biology Meetings in Shanghai
    • Place of Presentation
      Shanghai (China)
    • Year and Date
      2016-03-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Synthetic Molecules for Detecting and Eliminating Human Pluripotent Stem Cells2016

    • Author(s)
      Uesugi, M.
    • Organizer
      ABC2016 - 6th Special Meeting on ABC Proteins
    • Place of Presentation
      Innsbruck (Austria)
    • Year and Date
      2016-03-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 生理活性化合物の新しい世界2016

    • Author(s)
      上杉 志成
    • Organizer
      第108回分子科学フォーラム 市民公開講座
    • Place of Presentation
      岡崎コンファレンスセンター(愛知県岡崎市)
    • Year and Date
      2016-02-05
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Synthetic Molecules for Eliminating Human Pluripotent Stem Cells2016

    • Author(s)
      Uesugi, M.
    • Organizer
      ACBI 2016 Jakarta Meeting
    • Place of Presentation
      Jakarta (Indonesia)
    • Year and Date
      2016-01-29
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Synthetic Molecules for Cell Biology and Cell Therapy2016

    • Author(s)
      Uesugi, M.
    • Organizer
      The 8th Takeda Science Foundation Symposium on PharmaSciences
    • Place of Presentation
      武田薬品工業(株) 研修所(大阪府吹田市)
    • Year and Date
      2016-01-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Small Molecule Tools for Cell Biology and Cell Therapy2015

    • Author(s)
      Uesugi, M.
    • Organizer
      Pacifichem 2015 Natural Product-based Drug Discovery
    • Place of Presentation
      Honolulu (USA)
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Small Molecules That Modulate Protein Assemblies2015

    • Author(s)
      Uesugi, M.
    • Organizer
      Pacifichem 2015 Synthetic Modulators of Protein-Protein Interactions
    • Place of Presentation
      Honolulu (USA)
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 細胞を操る合成化合物2015

    • Author(s)
      上杉 志成
    • Organizer
      岡崎統合バイオサイエンスセンター 生命時空間設計研究領域 心循環シグナル研究部門公開セミナー
    • Place of Presentation
      岡崎統合バイオサイエンスセンター(愛知県岡崎市)
    • Year and Date
      2015-12-12
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 嫌いなものにチャンスがある!:ケミカルバイオロジーとは?2015

    • Author(s)
      上杉 志成
    • Organizer
      BMB2015市民公開講座
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-12-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Synthetic Molecules for Detecting and Eliminating Human Pluripotent Stem Cells2015

    • Author(s)
      Uesugi, M.
    • Organizer
      NEA & ASIAHORCs Joint Symposium - Chemical Biology - in Okinawa
    • Place of Presentation
      沖縄科学技術大学院大学(沖縄県国頭郡)
    • Year and Date
      2015-11-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Synthetic Molecules for Detecting and Eliminating Human Pluripotent Stem Cells2015

    • Author(s)
      Uesugi, M.
    • Organizer
      XVII NOST-Organic Chemistry Conference
    • Place of Presentation
      Jaipur (India)
    • Year and Date
      2015-10-27
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Small Molecule Tools for Cell Biology and Cell Therapy2015

    • Author(s)
      Uesugi, M.
    • Organizer
      2015 Fall Annual Convention of Pharmaceutical Society of Korea
    • Place of Presentation
      Daegu (Korea)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Synthetic Molecules for Cell Biology and Cell Therapy2015

    • Author(s)
      Uesugi, M.
    • Organizer
      AIMECS 2015 (10th AFMC International Medicinal Chemistry Symposium in 2015)
    • Place of Presentation
      Jeju (Korea)
    • Year and Date
      2015-10-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 生理活性合成化合物のケミカルバイオロジーが開く新しい世界2015

    • Author(s)
      上杉 志成
    • Organizer
      日本化学会秋季事業- 第5回CSJ化学フェスタ2015
    • Place of Presentation
      タワーホール船堀(東京都江戸川区)
    • Year and Date
      2015-10-15
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Synthetic Molecules for Cell Biology and Cell Therapy2015

    • Author(s)
      Uesugi, M.
    • Organizer
      IUPAC2015
    • Place of Presentation
      Busan (Korea)
    • Year and Date
      2015-08-10
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] くすりの形2015

    • Author(s)
      上杉 志成
    • Organizer
      京都大学化学研究所 第18回高校生のための化学
    • Place of Presentation
      京都大学宇治キャンパス(京都府宇治市)
    • Year and Date
      2015-07-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 細胞治療を助ける合成化合物2015

    • Author(s)
      上杉 志成
    • Organizer
      第52回薬剤学懇談会研究討論会
    • Place of Presentation
      瑠璃光(石川県加賀市)
    • Year and Date
      2015-07-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Synthetic Molecules for Cell Biology and Cell Therapy2015

    • Author(s)
      Uesugi, M.
    • Organizer
      The 51th International Conference on Medicinal Chemistry (RICT 2015) - "Drug Discovery and Selection - Understanding Targets and Mechanisms
    • Place of Presentation
      Avignon (France)
    • Year and Date
      2015-07-01
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 細胞を操作する合成化合物2015

    • Author(s)
      上杉 志成
    • Organizer
      第10回理研シンポジウム:第10回有機合成化学のフロンティア
    • Place of Presentation
      理化学研究所和光事業所(埼玉県和光市)
    • Year and Date
      2015-06-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 脂質関連内因性分子の新機能発掘と調節2015

    • Author(s)
      上杉 志成
    • Organizer
      新学術領域研究「天然物ケミカルバイオロジー~分子標的と活性制御~」第8回公開シンポジウム
    • Place of Presentation
      東北大学片平キャンパス(宮城県仙台市)
    • Year and Date
      2015-06-08
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 細胞を操作・検出する合成小分子化合物2015

    • Author(s)
      上杉 志成
    • Organizer
      「生物医工学サロン」第55回集会
    • Place of Presentation
      京都大学(京都市)
    • Year and Date
      2015-05-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Introduction of Chemical Biology2015

    • Author(s)
      Motonari Uesugi
    • Organizer
      Cell Biology, Developmental Biology, and Systems Biology Course Meeting
    • Place of Presentation
      Kyoto (Japan)
    • Year and Date
      2015-02-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 細胞を操作・検出する合成小分子化合物2015

    • Author(s)
      上杉 志成
    • Organizer
      近畿化学協会機能性色素部会 第88回例会「未来をつくる機能性色素・・・その技術と応用・・・」
    • Place of Presentation
      大阪科学技術センター(大阪市)
    • Year and Date
      2015-02-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Introduction to Chemical Biology2014

    • Author(s)
      Motonari Uesugi
    • Organizer
      Asian Chemical Biology Initiative 2014 Kota Kinabalu Meeting: Open Tutorial Lectures
    • Place of Presentation
      Kota Kinabalu (Malaysia)
    • Year and Date
      2014-12-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Small Molecule Tools for Cell Biology and Cell Therapy2014

    • Author(s)
      Motonari Uesugi
    • Organizer
      Institute of Molecular and Cell Biology Seminar
    • Place of Presentation
      Singapore (Singapore)
    • Year and Date
      2014-12-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Small Molecule Tools for Cell Therapy2014

    • Author(s)
      Motonari Uesugi
    • Organizer
      The 3rd Asian Chemical Biology Conference
    • Place of Presentation
      Singapore (Singapore)
    • Year and Date
      2014-12-15 – 2014-12-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Small Molecule Tools for Cell Biology and Cell Therapy2014

    • Author(s)
      Motonari Uesugi
    • Organizer
      Nanjing University School of Life Sciences Seminar
    • Place of Presentation
      Nanjing (China)
    • Year and Date
      2014-11-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Small Molecule Tools for Cell Biology and Cell Therapy2014

    • Author(s)
      Motonari Uesugi
    • Organizer
      Asian Chemical Biology Initiative 2014 Hangzhou Meeting
    • Place of Presentation
      Hangzhou (China)
    • Year and Date
      2014-11-22 – 2014-11-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Small Molecule Tools for Cell Biology and Cell Therapy2014

    • Author(s)
      Motonari Uesugi
    • Organizer
      Chinese National Compound Library 2014 Seminar Series
    • Place of Presentation
      Shanghai (China)
    • Year and Date
      2014-11-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] New Functions of Endogenous Lipid Molecules and Their Modulation2014

    • Author(s)
      Motonari Uesugi
    • Organizer
      The 3rd International Symposium on Chemical Biology of Natural Products
    • Place of Presentation
      Osaka (Japan)
    • Year and Date
      2014-10-28 – 2014-10-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] Small MoleculesThat Detect and Remove Human Pluripotent Stem Cells2014

    • Author(s)
      Motonari Uesugi
    • Organizer
      Sino-Japan Workshop on Chemical Biology
    • Place of Presentation
      Beijing (China)
    • Year and Date
      2014-10-10 – 2014-10-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Small Molecule Tools That Detect and Remove Human Pluripotent Stem Cells2014

    • Author(s)
      Motonari Uesugi
    • Organizer
      China-Japan Joint Seminar on Histochemistry and Cytochemistry
    • Place of Presentation
      Nagano (Japan)
    • Year and Date
      2014-09-28 – 2014-09-29
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Small Molecule Tools for Cell Therapy2014

    • Author(s)
      Motonari Uesugi
    • Organizer
      Forth Norman Bethune International Forum on Medical Sciences
    • Place of Presentation
      Jilin (China)
    • Year and Date
      2014-09-20 – 2014-09-24
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 生理活性合成化合物の新しい世界2014

    • Author(s)
      上杉 志成
    • Organizer
      第31回有機合成化学セミナー
    • Place of Presentation
      休暇村志賀島(福岡市)
    • Year and Date
      2014-09-17 – 2014-09-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 細胞を操作・検出する合成小分子化合物2014

    • Author(s)
      上杉 志成
    • Organizer
      東京農工大学工学府講演会
    • Place of Presentation
      東京農工大学(小金井市)
    • Year and Date
      2014-07-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 細胞治療を助ける合成化合物2014

    • Author(s)
      上杉 志成
    • Organizer
      創薬科学研究センターシンポジウム2014有機合成によるアンメット・メディカルニーズに応える医薬品開発
    • Place of Presentation
      立命館大学(草津市)
    • Year and Date
      2014-07-11
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Introduction of Chemical Biology & Small-Molecule Tools for Cell Biology and Cell Therapy2014

    • Author(s)
      Motonari Uesugi
    • Organizer
      Asian Chemical Biology Initiative-Sponsored Lectures
    • Place of Presentation
      Hanoi (Vietnam)
    • Year and Date
      2014-07-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Small Molecule Tools for Cell Biology and Cell Therapy2014

    • Author(s)
      Motonari Uesugi
    • Organizer
      The University of Tokyo School of Science 1527th Seminar
    • Place of Presentation
      Tokyo (Japan)
    • Year and Date
      2014-06-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 脂質合成を遮断する小分子化合物2014

    • Author(s)
      上杉 志成
    • Organizer
      小野医学研究財団 第25回研究成果発表会
    • Place of Presentation
      千里ライフサイエンスセンター(豊中市)
    • Year and Date
      2014-06-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 脂質関連内因性分子の新機能発掘と調節2014

    • Author(s)
      上杉 志成
    • Organizer
      新学術領域研究「天然物ケミカルバイオロジー~分子標的と活性制御~」第6回公開シンポジウム
    • Place of Presentation
      名古屋大学(名古屋市)
    • Year and Date
      2014-05-28 – 2014-05-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] Small Molecules that Block Fat Synthesis2014

    • Author(s)
      Motonari Uesugi
    • Organizer
      RIKEN-Max Planck Joint Research Center for Systems Chemical Biology 3rd Annual Symposium
    • Place of Presentation
      Kreuth (Germany)
    • Year and Date
      2014-05-21 – 2015-05-24
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Book] ビオチン化体を利用した生化学的標的タンパク質精製法2015

    • Author(s)
      佐藤慎一、勝田陽介、上杉志成
    • Total Pages
      5
    • Publisher
      化学同人
    • Related Report
      2015 Annual Research Report
  • [Remarks] 京都大学iCeMS・化学研究所 上杉研究室

    • URL

      http://www.scl.kyoto-u.ac.jp/~uesugi/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 京都大学物質-細胞統合システム拠点・化学研究所 上杉研究室

    • URL

      http://www.scl.kyoto-u.ac.jp/~uesugi/

    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] VITAMIN D3 DERIVATIVES AND PHARMACEUTICAL USE THEREOF2015

    • Inventor(s)
      渡邉瑞貴、浅野理沙、長澤和夫、上杉志成
    • Industrial Property Rights Holder
      国立大学法人京都大学、国立大学法人東京農工大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-12-24
    • Related Report
      2015 Annual Research Report
    • Overseas

URL: 

Published: 2014-04-04   Modified: 2023-03-16  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi