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DEVELOPMENT OF FUNCTIONAL FLUORESCENT PROBES FOR BIOIMAGING

Research Project

Project/Area Number 12557217
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 医薬分子機能学
Research InstitutionThe University of Tokyo

Principal Investigator

NAGANO Tetsuo  THE UNIVERSITY OF TOKYO, GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, PROFESSOR, 大学院・薬学系研究科, 教授 (20111552)

Co-Investigator(Kenkyū-buntansha) URANO Yasuteru  THE UNIVERSITY OF TOKYO, GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, RESEARCH ASSOCIATE, 大学院・薬学系研究科, 助手 (20292956)
KIKUCHI Kazuya  THE UNIVERSITY OF TOKYO, GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, ASSOCIATE PROFESSOR, 大学院・薬学系研究科, 助教授 (70292951)
HIGUCHI Tsunehiko  NAGOYA CITY UNIVERSITY, FACULTY OF PHARMACEUTICAL SCIENCES, PROFESSOR, 薬学部, 教授 (50173159)
SHIMADA Noriaki  DAIICHI PURE CHEMICALS, CO Ltd., RAW MATERIAL LABORATORY, CHIEF MANAGER (RESEARCHER), 素材技術研究所, 所長(研究職)
HIRATA Yasunobu  THE UNIVERSITY OF TOKYO, GRADUATE SCHOOL OF MEDICINE, LECTURER, 大学院・医学系研究科, 講師 (70167609)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2002: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥5,300,000 (Direct Cost: ¥5,300,000)
Keywordshighly reactive oxygen species / bioimaging / fluorescence / inflammation / probe / neutrophiles / photoinduced electron transfer / 亜鉛 / 蛍光顕微鏡 / 虚血 / 錯体
Research Abstract

Human beings are highly receptive to an enormous amount and variety of information from the external environment, and more than 90 % of it is thought to be visual. It is generally said that an appeal to the eye is more effective than that to the ear, which may be the basis of the proverb "Seeing is believing". To be able to "see into the body" or "see into cells" is essential in the diagnosis and treatment of disease, as well as for research into the basic processes of life. Moreover, it is desirable that seeing into the body and cells is accomplished by using noninvasive techniques, without cutting into the body or isolating of cellular constituents. Therefore, we believe that techniques to visualize physiological or pathophysiological changes in the body and cells become increasingly important in biomedical sciences. In this research project, we have developed the chemical probes for bioimaging of biological active compounds; nitric oxide, zinc ion, singlet oxygen, highly reactive oxygen species, magnesium ion, anion, caspase, protein tyrosine phosphatase and phosphodiesterase, based on the mechanisms of photoinduced electron transfer (PET) and fluorescence resonance energy transfer (FRET). These probes were applied to living cells and tissue cultures in order to evaluate bio-functions of the biological active compounds. As the results, we obtained the results that these probes are in practical use and can reveal numerous roles of the biological active compounds in various biological systems.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (45 results)

All Other

All Publications (45 results)

  • [Publications] Ken-ichi Setsukinai: "Development of Novel Fluorescence Probes That Can Reliably Detect Reactive Oxygen Species and Distinguish Specific Species"J. Biol. Chem.. 278. 3170-3175 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Satoko Maruyama: "A novel, cell-permeable, fluorescent probe for ratiometric imaging of zinc ion"J. Am. Chem. Soc.. 124. 10650-10651 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sayaka Ueno: "Mossy Fiber Zn^<2+> Spillover Modulates Heterosynaptic N-methyl-D-aspartate Receptor Activity in Hippocampel CA3 Circuits"J. Cell Biology. 158. 215-220 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomoya Hirano: "Improved Fluorescent Probes for Zinc, ZnAFs, Suitable for Biological Applications"J. Am. Chem. Soc.. 124. 6555-6562 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shin Mizukami: "A Fluorescent Anion Sensor That Works in Neutral Aqueous Solution for Bioanalytical Application"J. Am. Chem. Soc.. 124. 3920-3925 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hideo Takakusa: "Design and Synthesis of an Enzyme-Cleavable Sensor Molecule for Phosphodiesterase Activity Based on Fluorescence Resonance Energy Transfer"J. Am. Chem. Soc.. 124. 1653-1657 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tetsuo Nagano: "Bioimaging of Nitric Oxide"American Chemical Society. 1235-1270 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kenjiro Hanaoka, Kazuya Kikuchi, Hirotatsu Kojima, Yasuteru Urano, and Tetsuo Nagano: "Selective Detecting of Zinc Ions with Novel Luminescent Lanthanide Probes"Angewandte Chemie, Int. Ed.. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takanari Inoue, Kazuya Kikuchi, Kenzo Hirose, Masamitsu Iino, and Tetsuo Nagano: "Spatiotemporal Laser Inactivation of Inositol 1,4,5-Trisphosphate Receptors Using Synthetic Small-molecule Probes"Chemistry & Biology. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takuji Shoda, Kazuya Kikuchi, Hirotatsu Kojima, Yasuteru Urano, Hirokazu Komatsu, Koji Suzuki, and Tetsuo Nagano: "Development of Selective, Visible Light-excitable, Fluorescent Magnesium Probes with a Novel Fluorescence Switching Mechanism"The Analyst. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hideo Takakusa, Kazuya Kikuchi, Yasuteru Urano, Hirotatsu Kojima, and Tetsuo Nagano: "A Novel Design Method of Ratiometric Fluorescent Probes Based on Fluorescence Resonance Energy Transfer Switching by Spectral Overlap Integral"Chemistry-A European Journal. 9. 1479-1485 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ken-ichi Setsukinai, Yasuteru Urano, Katsuko Kakinuma, Hideyuki J. Majima, and Tetsuo Nagano: "Development of Novel Fluorescence Probes That Can Reliably Detect Reactive Oxygen Species and Distinguish Specific Species"J. Biol Chem.. 278. 3170-3175 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahiro Kitano, Shinji Matsumura, Toshihito Seki, Takatoshi Hikida, Kenji Sakimura, Tetsuo Nagano, Masayoshi Mishina, Shigetada Nakanishi, and Seiji Itoh: "Characterization of N-methyl-D-aspartate Receptor Subunits Involved in Acute Ammonia Toxicity"Neurochem. Int.. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamaki Mabuchi, Shinji Matsumura, Emiko Okuda-Ashitaka, Takahiro Kitano, Hirotatsu Kojima, Foo Y. Liew, Tetsuo Nagano, Toshiaki Minami, and Seiji Ito: "Attenuation of Neuropathic Pain by Nociceptin/Orphanin FQ Antagonist is Mediated by Inhibition of Nitric Oxide Production"Eur. J. Neuroscl. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nobuhiro Nishiyama, Hendrik R. Stapert, Guo-Dong Zhang, Daisuke Takasu, Dong-Lin Jiang, Tetsuo Nagano, Takuzo Aida, and Kazunori Kataoka: "Light-Harvesting Ionic Dendrimer Porphyrins as New Photosensitizes for Photodynamic Therapy"Bioconjugate Chemistry. 14. 58-88 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kenjiro Hanaoka, Kazuya Kikuchi, Yasuteru Urano, Michiko Narazaki, Takashi Yokawa, Shigeru Sakamoto, Kentaro Yamaguchi, and Tetsuo Nagano: "Design and synthesis of a novel magnetic resonance imaging contrast agent for selective sensing of zinc ion"Chemistry and Biology. 9. 1027-1032 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S. Maruyama, K. Kikuchi, T. Hirano, Y. Urano, and T. Nagano: "A Novel, Cell-Permeable, Fluorescent Probe for Ratiometric Imaging of Zinc Ion"J. Am. Chem. Sac.. 124. 10650-10651 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noriyuki Suzuki, Tsunehiko Higuchi, and Tetsuo Nagano: "Multiple Active Intermediates in Oxidation Reaction Catalyzed by Synthetic Heme-thiolate Complex Relevant to Cytochrome P450"J. Am. Chem. Soc.. 124. 9622-9628 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sayaka Ueno, Masako Tsukamoto, Tomoya Hirano, Kazuya Kikuchi, Maki K. Yamada, Nobuyoshi Nishiyama, Tetsuo Nagano, Norio Matsuki, and Yuji Ikegaya: "Mossy Fiber Zn2+ Spillover Modulates Heterosynaptic N-methyl-D-aspartate Receptor Activity in Hippocampel CA3 Circuits"J. Cell Biology. 158. 215-220 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomoya Hirano, Kazuya Kikuchi, Yasuteru Urano, and Tetsuo Nagano: "Improved Fluorescent Probes for Zinc, ZnAFs, Suitable for Biological Applications"J. Am. Chem. Soc.. 124. 6555-6562 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ken-ichi Setsukinai: "Development of Novel Fluorescence Probes That Can Reliably Detect Reactive Oxygen Species and Distinguish Specific Species"J. Biol. Chem.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Satoko Maruyama: "A Novel, Cell-permeable, Fluorescent Probe for Ratiometric Imaging of Zinc Ion"J. Am. Chem. Soc.. 124. 10650-10651 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sayaka Ueno: "Mossy Fiber Zn^<2+> Spillover Modulates Heterosynaptic N-methyl-D-aspartate Receptor Activity in Hippocampel CA3 Circuits"J. Cell Biology. 158. 215-220 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tomoya Hirano: "Improved Fluorescent Probes for Zinc, ZnAFs, Suitable for Biological Applications"J. Am. Chem. Soc.. 124. 6555-6562 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shin Mizukami: "A Fluorescent Anion Sensor That Works in Neutral Aqueous Solution for Bioanalytical Application"J. Am. Chem. Soc.. 124. 3920-3925 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hideo Takakusa: "Design and Synthesis of an Enzyme-Cleavable Sensor Molecule for Phosphodiesterase Activity Based on Fluorescence Resonance Energy Transfer"J. Am. Chem. Soc.. 124. 1653-1657 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tetuo Nagano: "Bioimaging of Nitric Oxide"American Chemical Society. 1653-1657 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Motohiro Nishida: "Gi and Go as a Redox Sensor"J.Biol.Chem.. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Hideo Takakusa: "Design and Synthesis of an Enzyme-Cleavable Sensor Molecule for Phosphodiesterase Activity Based on FRET"J.Am.Chem.Soc.. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Noriyuki Suzuki: "Orthogonality of Calcium Concentration and Ability of 4, 5-Diaminofluorescein to Detect NO"J.Biol.Chem.. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Kuni Tanaka: "Rational Design of Fluorescein-bared Fluorescence Probes-Mechanism-based Design of a Maximum Fluorescence Probe for ^iO_2"J.Am.Chem.Soc.. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirotatsu Kojima: "Bioimaging of Nitric oxide with Fluorescent Indicators Bared on Rhodamine Chromophore"Anal.Chem.. 73. 1967-1973 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takanari Inoue: "Small Molecule-based Laser Inactivation of Inositol 1, 4, 5-Triphosphate Receptor"Chemistry and Biology. 8. 9-15 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tomoya Hirano: "Novel Zinc Fluorescent Probes Excitable with Visible Light for Biological Applications"Angewandte Chemie, Int.Ed.. 39. 1052-1054 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mitsunori Koresawa: "Development of Time-resolved Fluorometric Detection System Using Diffusion-enhanced Energy Transfer"Analytical Chemistry. 72. 4904-4907 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasutomo Kawanishi,: "Design and Synthesis of Intramolecular Resonance Energy Transfer Probes for Use in Aqueous Solution"Angewandte chemie, Int.Ed.. 39. 3438-3440 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tomoya Hirano: "Highly Zinc-Selective Fluorescent Sensor Molecules Suitable for Biological Applications"J.Am.Chem.Soc.. 122. 12399-12400 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Noriyuki Suzuki: "First Synthetic NO-heme-thiolate Complex Relevant to Nitric Oxide Synthase and Cytochrome P450nor"J.Am.Chem.Soc.. 122. 12059-12062 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ken-ichi Setsukinai: "Fluorescence Switching by O-dearylation of 7-Aryloxycoumarines.-Development of Novel Fluorescence Probes to Detect Reactive Oxygen Species with High Selectivity-"J.Chem.Soc., Perkin Transaction 2. 2453-2457 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshinori Itoh: "Determination and Bioimaging Method for Nitric Oxide in Biological Specimens by Diaminofluorescein Fluorometry"Analytical Biochemistry. 287. 203-209 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hideo Takakusa: "Intramolecular Fluorescence Resonance Energy Transfer System with Coumarin Donor Induced in β-Cyclodextrin"Analytical chemistry. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirotatsu kojima: "Visualization of Oxygen Concentration-dependent Production of Nitric Oxide in Rat Hippocampal Slices during Aglycemia"J.Neurochem.. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Takanari Inoue: "Small Molecule-based Laser Inactivation of Inositol 1, 4, 5-Triphoaphate Receptor"Chemistry and Biology. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirotatsu Kojima: "Bioimaging of Nitric Oxide with Fluorescent Indicators Based on Rhodamine Chromophore"Analytical Chemistry. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Kumi Tanaka: "Rational Design of Fluorescein-based Fluorescence Probes.-Mechanism-based Design of a Maximum Fluorescence Probe for Singlet Oxygen-"J.Am.Chem.Soc.. (in press).

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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