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

Development of Bio-imaging Probes for Morbidity

Research Project

Project/Area Number 11794026
Research Category

Grant-in-Aid for University and Society Collaboration

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

Principal Investigator

NAGANO Tetsuo  Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学系研究科, 教授 (20111552)

Co-Investigator(Kenkyū-buntansha) SHIMADA Noriaki  Daiichi Chemical Co. Ltd., Synthetic Laboratory, General Manager (Researcher), 素材技術研究所, 所長(研究職)
HIRATA Yasunobu  Graduate School of Medicine, Lecturer, 大学院・医学系研究科, 教授 (70167609)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥9,900,000 (Direct Cost: ¥9,900,000)
Fiscal Year 2001: ¥9,900,000 (Direct Cost: ¥9,900,000)
Keywordsprobe / bio-imaging / MRI / zincion / neurotransfer / relaxation / fertilization / プローグ / 受精 / 一酸化窒素
Research Abstract

The MRI image is based upon the NMR signal from the protons of water, and the Signal intensity depends upon the water concentration and relaxation times. Nowadays, there is great interest in MRI contrast agents, which can improve the resolution of MR images. Gadolinium complexes are widely used as contrast agents for MRI.
On the other hand, Zn^<2+> is the second most abundant heavy metal ion after iron in the human body. It is an essential component of many enzymes, transcription factors, and synaptic vesicles in excitatory nerve terminals and is present in serum at a concentration of 〜12 μM (total Zn^<2+>). Recently, Zn^<2+> has been reported to play important roles in regulating synaptic transmission and cell death. Therefore, imaging of chelatable Zn^<2+> in the extra- and intracellular environments or in tissues is of interest. A series of new diethylenetriaminepentaacetic acid (DTPA)-bisamide chelators has been prepared and characterized for application as Zn^<2+> sensors. We have designed and synthesized (GdL)^<2->, which contains a DTPA-bisamide moiety. The R_1 relaxivity of (GdL)^<2-> solution decreased monotonically on the addition of Zn^<2+>. Moreover, (GdL)^<2-> showed high selectivity for Zn^<2+> against Ca^<2+> and Mg^<2+>. These complexes should provide the basis for creating a superior Zn^<2+> sensitive MRI contrast agent and are excellent candidates for incorporation into sensors designed for selective detection of Zn^<2+> in biological applications.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] Tetsuo Nagano: "Bioimaging of Nitric Oxide"Chemical Reviews. 102. 1235-1270 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kenjiro Hanaoka: "Design and Symthesis of a Novel Magnetic Resonance Imaging Contrast Agent for Selective Sensing of Zinc Ion"Chemical and Biology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Satoko Maruyama: "A Novel Cell-Permeable, Fluorescent Probe for Ratiometric Imaging of Zinc Ion"J. Am. Chem. Soc.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sayaka Ueno: "Mossy Fiber Zn^<2+> Spillover Modulates Heterosynaptic N-methyl-D-aspartate Receptor Activity in Hippocampal CA3 Circuits"Cell Biology. 158. 215-220 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 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
      2001 Final Research Report Summary
  • [Publications] Noriyuki Sizuki: "Orthogonality of Calcium Concentration and Ability of 4,5-Diamino-fluoresein (DAF-2) to Detect NO"J. Biol. Chem.. 277. 47-49 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 菊地和也: "化学と生物"学会出版センター. 549-553 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tetsuo Nagano and Tetsuhiko Yoshimura: "Bioimaging of Nitric Oxide"Chemical Reviews. 102. 1235-1270 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 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. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S.Maruyama, K Kikuchi, T Hirano, Y.Urano, T.Nagano: "A Novel, Cell-Permeable, Fluorescent Probe for Ratiometric Imaging of Zinc Ion"J.Am.Chem.Soc.. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 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 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(欧文)」より
    • Related Report
      2001 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
      2001 Final Research Report Summary
  • [Publications] Noriyuki Suzuki, Hirotatsu Kojima, Yasuteru Urano, Kazuya Kikuchi, Yasunobu Hirata and Tetsuo Nagano: "Orthogonality of Calcium Concentration and Ability of 4,5-Diaminofluorescein (DAF-2) to Detect NO"J.Biol.Chem.. 277. 47-49 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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-based Fluorescence Probes. -Mechanism-based Design of a Maximum Fluorescence Probe for 'O_2"J.Am.Chem.Soc.. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirotatsu Kojima: "Bioimaging of Nitric oxide with Fluorescent Indicators Based 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-Trisphosphate 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
  • [Publications] Takanari Inoue: "Synthesis and Evaluations of 1-position-modified Inositol 1,4,5-Triphosphate Analogs"Bioorganic & Medicinal Chemistry Letters. 9. 1697-1702 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Naoki Umezawa: "Novel Fluorescent Probe for Singlet Oxygen"Angewandte Chemie Int. Ed.. 38. 2899-2901 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hirotatsu Kojima: "Fluorescent Indicators for Imaging Nitric Oxide Production"Angewandte Chemie Int. Ed.. 38. 3209-3212 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Noriyuki Suzuki: "Novel Iron Porphyrin-alkanethiolate Complex with Intramolecular NH … S Hydrogen Bond : Synthesis, Spectroscopy and Reactivity"J. Am. Chem. Soc.,. 121. 11571-11572 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hirotatsu Kojima: "Fluorescent Indicators for Nitric Oxide Based on Rhodamine Chromophore"Tetrahedron Letters. 41. 69-72 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tetsuo Nagano: "Practical Methods of Detection of Nitric Oxide"Luminescence. 14. 283-290 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 小島宏建: "実験医学"羊土社 (分担執筆). 946-950 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 長野哲雄: "現代化学"東京化学同人(分担執筆). 23-30 (1999)

    • Related Report
      1999 Annual Research Report

URL: 

Published: 2001-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi