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2012 Fiscal Year Final Research Report

Development of novel fluorescence probes and imaging technologies for elucidating the mechanism of cellular signaling and responses induced by ROS

Planned Research

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Project AreaSignaling functions of reactive oxygen species
Project/Area Number 20117003
Research Category

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

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

URANO Yasuteru  東京大学, 大学院・医学系研究科, 教授 (20292956)

Project Period (FY) 2008 – 2012
Keywords蛍光プローブ / 活性酸素種 / シグナル / 親電子性活性種 / イメージング
Research Abstract

For elucidating the functions of ROS and RNS as intracellular signaling molecules, we aimed at developing novel optical imaging probes which afford their live-imaging in living biological samples. We have succeeded in developing fluorescence probes for hydrogen peroxide, acrolein, and the enzymatic activity of glutathione S-transferase, those for highly ROS and NO which has much desired property of intracellular retention for the long-period observation, that for hypochlorite with NIR emitting capability, and luminescence probes for detecting hROS. We also have succeeded to obtain various striking images of each ROS and RNS in living cells and animals.

  • Research Products

    (48 results)

All 2013 2012 2011 2010 2009 2008

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (30 results) Book (2 results)

  • [Journal Article] Rational Design of Highly Sensitive Fluorescence Probes For Protease and Glycosidase Based on Precisely Controlled Spirocyclization2013

    • Author(s)
      Sakabe M, Asanuma D, Kamiya M, Iwatate JR, Hanaoka K, Terai T, Nagano T, Urano Y
    • Journal Title

      J. Am. Chem. Soc

      Volume: 135 Pages: 409-14

    • DOI

      doi:10.1021/ja309688m

    • Peer Reviewed
  • [Journal Article] Rational Design and Development of Near-Infrared-Emitting Firefly Luciferins Available In Vivo2012

    • Author(s)
      Kojima R, Takakura H, Ozawa T, Tada Y, Nagano T, Urano Y
    • Journal Title

      Angew Chem Int Ed Engl

      Volume: 52 Pages: 1175-1179

    • DOI

      doi:10.1002/anie.201205151

    • Peer Reviewed
  • [Journal Article] Novel live imaging techniques of cellular functions and in vivo tumors based on precise design of small molecule-based 'Activatable' fluorescence probes2012

    • Author(s)
      Urano Y
    • Journal Title

      Current Opinion in Chemical Biology

      Volume: 16 Pages: 602-608

    • DOI

      doi:10.1016/j.cbpa.201210023

    • Peer Reviewed
  • [Journal Article] Highly Activatable and Environment-insensitive Optical Highlighters for Selective Spatiotemporal Imaging of Target Proteins2012

    • Author(s)
      Kobayashi T, Komatsu T, Kamiya M, Campos C, Gonzalez-Gaitan M, Terai T, Hanaoka K, Nagano T, Urano Y
    • Journal Title

      J. Am. Chem. Soc

      Volume: 134 Pages: 11153-11160

    • DOI

      doi:10.1021/ja212125w

    • Peer Reviewed
  • [Journal Article] Development of NIR fluorescent dyes based on Si-rhodamine for in vivo imaging2012

    • Author(s)
      Koide Y, Urano Y, Hanaoka K, Piao W, Kusakabe M, Saito N, Terai T, Okabe T, Nagano T
    • Journal Title

      J Am Chem Soc

      Volume: 134 Pages: 5029-31

    • DOI

      doi:10.1021/ja210375e

    • Peer Reviewed
  • [Journal Article] "Activatable"蛍光プローブの開発に基づく高感度術中がん部位検出の実現2012

    • Author(s)
      浦野泰照
    • Journal Title

      薬学雑誌

      Volume: 132 Pages: 397-406

    • DOI

      doi:10.1248/yakushi.132.397

    • Peer Reviewed
  • [Journal Article] Rapid Cancer Detection by Topically Spraying a Gamma-glutamyltranspeptidase-activated Fluorescent Probe2011

    • Author(s)
      Urano Y, Sakabe M, Nobuyuki Kosaka, Ogawa M, Mitsunaga M, Asanuma D, Kamiya M, Young MR, Nagano T, Choyke PL, Kobayashi H
    • Journal Title

      Sci Transl Med

      Volume: 3 Pages: 110ra119

    • DOI

      doi:10.1126/scitranslmed.3002823

    • Peer Reviewed
  • [Journal Article] Improved Cellular Accumulation Based on Spirocyclized Rhodol Scaffold2011

    • Author(s)
      Kamiya M, Asanuma D, Kuranaga E, Takeishi A, Sakabe M, Miura M, Nagano T, Urano Y
    • Journal Title

      J. Am. Chem. Soc

      Volume: 133 Pages: 12960-12963

    • DOI

      doi:10.1021/ja204781t

    • Peer Reviewed
  • [Journal Article] Development of a highly sensitive fluorescence probe for hydrogen peroxide2011

    • Author(s)
      Abo M, Urano Y, Hanaoka K, Terai T, Komatsu T, Nagano T
    • Journal Title

      J. Am. Chem. Soc

      Volume: 133 Pages: 10629-10637

    • DOI

      doi:10.1021/ja203521e

    • Peer Reviewed
  • [Journal Article] Real-time measurements of protein dynamics using fluorescence activation-coupled protein labeling method2011

    • Author(s)
      Komatsu T, Johnsson K, Okuno H, Bito H, Inoue T, Nagano T, Urano Y
    • Journal Title

      J. Am. Chem. Soc

      Volume: 133 Pages: 6745-6751

    • DOI

      doi:10.1021/ja200225m

    • Peer Reviewed
  • [Journal Article] Development of an Si-rhodamine-based far-red to near-infrared fluorescence probe selective for hypochlorous acid and its applications for biological imaging2011

    • Author(s)
      Koide Y, Urano Y, Hanaoka K, Terai T, Nagano T
    • Journal Title

      J. Am. Chem. Soc

      Volume: 133 Pages: 5680-5682

    • DOI

      doi:10.1021/ja111470n

    • Peer Reviewed
  • [Journal Article] Sensitive Detection of Acrolein in Serum Using Time-resolved Luminescence2010

    • Author(s)
      Togashi M, Urano Y, Kojima H, Terai T, Hanaoka K, Igarashi K, Hirata Y, Nagano T
    • Journal Title

      Org. Lett

      Volume: 12 Pages: 1704-1707

    • DOI

      doi:10.1021/ol1002219

    • Peer Reviewed
  • [Journal Article] A simple and effective strategy to increase the sensitivity of fluorescence probes in living cells2009

    • Author(s)
      Izumi S, Urano Y, Hanaoka K, Terai T, Nagano T
    • Journal Title

      J. Am. Chem. Soc

      Volume: 131 Pages: 10189-10200

    • DOI

      doi:10.1021/ja902511p

    • Peer Reviewed
  • [Journal Article] Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes2009

    • Author(s)
      Urano Y, Asanuma D, Hama Y, Koyama Y, Barrett T, Kamiya M, Nagano T, Watanabe T, Hasegawa A, Choyke PL, Kobayashi H
    • Journal Title

      Nat. Med

      Volume: 15 Pages: 104-109

    • DOI

      doi:10.1038/nm.1854

    • Peer Reviewed
  • [Journal Article] Design and synthesis of highly sensitive fluorogenic substrates for glutathione S-transferase (GST) and application for activity imaging in living cells2008

    • Author(s)
      Fujikawa Y, Urano Y, Komatsu T, Hanaoka K, Kojima H, Terai T, Inoue H, Nagano T
    • Journal Title

      J. Am. Chem. Soc

      Volume: 130 Pages: 14533-14543

    • DOI

      doi:10.1021/ja802423n

    • Peer Reviewed
  • [Journal Article] Selective photoinactivation of protein function through environment-sensitive switching of singlet oxygen generation by photosensitizer2008

    • Author(s)
      Yogo T, Urano Y, Mizushima A, Sunahara H, Inoue T, Hirose K, Iino M, Kikuchi K, Nagano T
    • Journal Title

      Proc. Natl. Acad. Sci

      Volume: 105 Pages: 28-32

    • DOI

      doi:10.1073/pnas.0611717105

    • Peer Reviewed
  • [Presentation] 分子内spiro環化平衡の精密制御に基づく蛍光・増感プローブの開発とがん医療への応用2013

    • Organizer
      日本化学会第93春季年会特別企画講演
    • Place of Presentation
      滋賀(立命館大学)
    • Year and Date
      2013-03-25
  • [Presentation] In Vivo Rapid Cancer Detection by Topically Spraying a Novel γ-Glutamyltranspeptidase-activated Fluorescence Probe2013

    • Organizer
      VIPCA Chemical Biology: Methods and Progress
    • Place of Presentation
      Austria (Vienna)
    • Year and Date
      2013-02-12
  • [Presentation] Realtime imaging of ROS in living cells and tiny tumors in vivo by rationally designed novel fluorescence probes2012

    • Organizer
      Joint JSPS - Karolinska Institute Symposium
    • Place of Presentation
      Sweden (Karolinska Institute, Stockholm)
    • Year and Date
      2012-10-23
  • [Presentation] スマート蛍光プローブの精密開発による新たな細胞・疾患イメージング2012

    • Organizer
      第56回日本薬学会関東支部大会
    • Place of Presentation
      東京(昭和大学旗の台キャンパス)
    • Year and Date
      2012-10-13
  • [Presentation] 光機能性プローブの精密開発によるin vivo生物学・医療の新展開2012

    • Organizer
      BMAS2012
    • Place of Presentation
      東京(慶應義塾大学薬学部)
    • Year and Date
      2012-08-09
  • [Presentation] Real-time functional imaging of living cells and animals with rationally designed fluorescence probes2012

    • Organizer
      8th AFMC International Medicinal Chemistry Symposium
    • Place of Presentation
      Hokkaido (Chateraise Gateaux Kingdom Sapporo)
    • Year and Date
      2012-06-28
  • [Presentation] 新規有機小分子蛍光プローブの開発に基づく生細胞・動物個体内レドックスシグナルイメージング2012

    • Organizer
      第65回日本酸化ストレス学会
    • Place of Presentation
      徳島(徳島県郷土文化会館)
    • Year and Date
      2012-06-08
  • [Presentation] 新規有機小分子蛍光プローブの開発に基づく生細胞・動物個体内レドックスシグナルイメージング2012

    • Organizer
      日本薬学会第132年会 シンポジウム「レドックス制御研究の最前線」
    • Place of Presentation
      北海道(北海道大学)
    • Year and Date
      2012-03-29
  • [Presentation] 生細胞適用可能な光機能性分子の精密設計とその応用2012

    • Organizer
      日本化学会第92春季年会 シンポジウム「有機合成化学を起点とするものづくり戦略」
    • Place of Presentation
      神奈川(慶應義塾大学)
    • Year and Date
      2012-03-25
  • [Presentation] オリジナル蛍光プローブの精密設計による新たな生体イメージングの実現2011

    • Organizer
      第26回日本酸化ストレス学会関東支部会
    • Place of Presentation
      東京(東京工科大学鎌田キャンパス)
    • Year and Date
      2011-12-10
  • [Presentation] Frontier of Medicinal Science" (Invited), "Intraoperative Imaging of Tiny Tumor Sites with Rationally Designed Fluorescence Probes2011

    • Organizer
      8th AFMC International Medicinal Chemistry Symposium
    • Place of Presentation
      Tokyo (Keio Plaza Hotel)
    • Year and Date
      2011-11-30
  • [Presentation] Rational development of activatable fluorescence probes for in vivo medical imaging ~ Small molecule-based sensors for cancer detection ~2011

    • Organizer
      US-Japan Workshop on Bio-inspired Engineering of Next-generation Sensors and Actuators
    • Place of Presentation
      UC Berkeley (USA)
    • Year and Date
      2011-11-13
  • [Presentation] オリジナル蛍光プローブの精密設計による新たな生体イメージングの実現2011

    • Organizer
      第31回キャピラリー電気泳動研究会
    • Place of Presentation
      山形(慶応義塾大学鶴岡キャンパス)
    • Year and Date
      2011-11-09
  • [Presentation] ROS蛍光プローブを活用した新たな生細胞応答イメージング~ 画期的なイメージングを実現するためのTipsと注意点~2011

    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都(京都国際会議場)
    • Year and Date
      2011-09-24
  • [Presentation] Novel functional bioimaging techniques with rationally designed fluorescence probes2011

    • Organizer
      IUMS International Congress of bacteriology and Applied Microbiology
    • Place of Presentation
      Hokkaido (Sapporo Convention Center)
    • Year and Date
      2011-09-06
  • [Presentation] Live imaging of ROS, RNS and in vivo tiny tumors with rationally designed fluorescence probes2011

    • Organizer
      Joint Meeting of 5th Biennial Meeting of Society for Free Radical Research-Asia(SFRR-Asia), 8th Conference of Asian Society for Mitochondrial Research and Medicine(ASMRM), and 11th Conference of Japanese Society of Mitochondrial Research and Medicine(J-mit)
    • Place of Presentation
      Kagoshima (Kagoshima Citizens' Culture Hall)
    • Year and Date
      2011-09-03
  • [Presentation] 小分子蛍光プローブの精密開発に基づく生細胞・動物個体内ROS・RNSイメージング2011

    • Organizer
      第11回日本NO学会学術集会
    • Place of Presentation
      東京(昭和薬科大学)
    • Year and Date
      2011-05-13
  • [Presentation] オリジナル化学プローブの開発による、新たな生細胞観測、in vivoがんイメージングの実現2011

    • Organizer
      日本化学会第91回春季年会
    • Place of Presentation
      神奈川(神奈川大学)
    • Year and Date
      2011-03-27
  • [Presentation] Novel chemical fluorescence sensors for visualization of various ROS in living cells and animals2011

    • Organizer
      第84回日本薬理学会年会
    • Place of Presentation
      神奈川(パシフィコ横浜)
    • Year and Date
      2011-03-24
  • [Presentation] オリジナル化学プローブの開発による、新たな生細胞観測、in vivoがんイメージングの実現2010

    • Organizer
      第35回日本薬学会関東支部学術講演会
    • Place of Presentation
      東京(日本薬学会長井記念ホール)
    • Year and Date
      2010-11-13
  • [Presentation] 電子移動の精密制御による新たな生体応答観測・先進医療の実現2010

    • Organizer
      第43回酸化反応討論会
    • Place of Presentation
      東京(東京大学医学部鉄門講堂)
    • Year and Date
      2010-11-12
  • [Presentation] Selective Molecular Imaging of Viable Cancer Cells with Rationally Designed "Activatable" Fluorescence Probes2010

    • Organizer
      SPACC17
    • Place of Presentation
      Kagoshima (Kagoshima University)
    • Year and Date
      2010-10-14
  • [Presentation] 蛍光プローブの精密設計に基づく、新たな生細胞応答観測・in vivoがんイメージング2010

    • Organizer
      第21回日本生体防御学会シンポジウム「活性酸素の生体防御シグナルとバイオイメージング」
    • Place of Presentation
      宮城(仙台市戦災復興記念館)
    • Year and Date
      2010-07-24
  • [Presentation] オリジナル蛍光プローブ開発による新しい生体分子イメージング2010

    • Organizer
      第23回バイオメディカル分析科学シンポジウム シンポジウム 「in vivoイメージングと分析科学」
    • Place of Presentation
      宮城(ホテル松島大観荘)
    • Year and Date
      2010-07-23
  • [Presentation] Real-time imaging of various ROS, RNS and related enzymatic activities in living cells by using precisely designed novel fluorescence probes2010

    • Organizer
      The 6th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
    • Place of Presentation
      Kyoto (Kyoto International Conference Center)
    • Year and Date
      2010-06-15
  • [Presentation] Development of Novel Fluorescence Probes Based on Rational Design Strategies: Real-time Visualization of Various Cellular Responses and in vivo Tumor Imaging2009

    • Organizer
      ISBIE-2009
    • Place of Presentation
      Taipei
    • Year and Date
      2009-10-22
  • [Presentation] Rational design of novel fluorescence probes for visualizing various cellular responses and in vivo tumor imaging2009

    • Organizer
      4th Cell Stress Society International Congress on Stress Responses
    • Place of Presentation
      Sapporo
    • Year and Date
      2009-10-08
  • [Presentation] Rational design of novel fluorescence probes for visualizing various cellular responses and in vivo tumor imaging2009

    • Organizer
      European Conference on Chemistry for Life Sciences 2009
    • Place of Presentation
      Frankfurt, Germany
    • Year and Date
      2009-09-04
  • [Presentation] Real-time imaging of various ROS and enzymatic activity in living cells by using precisely developed novel fluorescence probes2009

    • Organizer
      International Symposium 2009 on Signaling Functions of Reactive Oxygen Species
    • Place of Presentation
      Kumamoto
    • Year and Date
      2009-07-18
  • [Presentation] 活性酸素シグナル応答機構の解明を目指した新規蛍光プローブ・イメージング技法の開発2009

    • Organizer
      レドックス研究とケミカルバイオロジーシンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2009-03-23
  • [Book] 種選択的高感度ROS・RNSイメージングを実現する有機小分子蛍光プローブ群の開発 細胞工学 312012

    • Author(s)
      浦野泰照
    • Total Pages
      187-193
    • Publisher
      学研メディカル秀潤社
  • [Book] 論理的設計法に基づく種選択的ROS蛍光プローブの開発 実験医学 27(15)2009

    • Author(s)
      浦野泰照
    • Total Pages
      2467-2473
    • Publisher
      羊土社

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Published: 2014-08-29  

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