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2001 Fiscal Year Final Research Report Summary

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
Keywordsprobe / bio-imaging / MRI / zincion / neurotransfer / relaxation / fertilization
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.

  • Research Products

    (13 results)

All Other

All Publications (13 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2004-04-14  

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