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短寿命励起鍵物質の蛍光発光原理解明と生細胞蛍光プローブへの応用

Research Project

Project/Area Number 13024217
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Science and Engineering
Research InstitutionThe University of Tokyo

Principal Investigator

菊地 和也  東京大学, 大学院・薬学系研究科, 助教授 (70292951)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywords蛍光プローブ / バイオイメージング / Zn^<2+>イオン / 励起状態 / 蛍光団 / 分子デザイン / 可視化 / 生細胞 / 海馬 / 虚血 / 蛍光図
Research Abstract

「生細胞プローブのデザイン・合成とその応用」.
生体内において,蛋白質に結合していない遊離のZn^<2+>は細胞死や神経伝達に関与していることが報告され,近年着目されるようになった.しかし,Zn^<2+>の作用機序に関しては不明な点が多い.そこで,Zn^<2+>を可視化することが,有効であると考え蛍光プローブの開発を行った.まず,PETの機構を用い,Zn^<2+>のホストを蛍光団に組み込むことで蛍光プローブを作成した.Zn^<2+>ホストとしてTPEN類縁体を用い,フルオレセインを蛍光団として用いZnAF類をデザイン・合成した.このうち,ZnAF-2はnMの濃度変化を測定でき,最高感度かつ選択的であり,ミリ秒単位での濃度変化を測定できる.さらに,細胞膜透過性に修飾したZnAF-2 DAを合成し,正常時及び虚血時におけるラット脳海馬におけるZn^<2+>濃度変化を可視化することに成功した.正常時,Zn^<2+>はCA3及び歯状回において高濃度で存在するが,虚血や脱分極刺激によってCA1において濃度上昇することを示した.これは生きた状態でのZn^<2+>濃度変化を可視化した初めての例である.

Report

(2 results)
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] T.Hirano, K.Kikuchi, Y.Urano, T.Nagano: "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] S.Mizukami, T.Nagano, Y.Urano, A.Odani, K.Kikuchi: "A Fluorescent Anion Sensor That Works in Neutral Aqueous Solution for Biological Application"J. Am. Chem. Soc.. 124. 3920-3925 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Takakusa, K.Kikuchi, Y.Urano, S.Sakamoto, K.Yamaguchi, T.Nagano: "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] 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.. 124. 10650-10656 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Haraoka, K.Kikuchi, Y.URANO, M.Narazaki, T.Yokawa, S.Sakamoto, K.Yamaguchi, T.Nagano: "Design and Synthesis of a Novel Magnetic Resonance Imaging Contrast Agent for Selective Sensing of Zinc Ion"Chem. Biol.. 9. 1027-1032 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Ueno, M.Tsukamoto, K.Kikuchi, M.K.Yamada, N.Nishiyama, T.Nagano, N.Matsuki, Y.Ikegaya: "Mossy Fiber Zn^<2+> Spillover Modulates Heterosynaptic N-methyl-D-aspartate Receptor Activity in Hippocampal CA3 Circuits"J. Cell. Biol.. 158. 215-220 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Hanaoka, K.Kikuchi, Y.Urano, T.Nagano: "Selective Sensing of Zinc Ion with A Novel Magnetic Resonance Imaging Contrast"J. Chem. Soc. Perkin. Trans. 2. 1840-1843 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Inoue, K.Kikuchi, K.Hirose, M.Iino, T.Nagano: "Small Molecule-based Laser Inactivation of Inositol 1,4,5-Trisphosphate Receptor"Chem. Biol.. 8. 9-15 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Takakusa, K.Kikuchi, Y.Urano, T.Higuchi, T.Nagano: "Intramolecular Fluorescence Resonance Energy Transfer System with Coumarin Donor Included in beta-Cyclodextrin"Anal. Chem.. 73. 1967-1973 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Kojima, M.Hirotani, N.Nakatsubo, K.Kikuchi, Y.Hirata, T.Nagano: "Bioimaging of Nitric Oxide with Fluorescent Indicators Based on Rhodamine Chromophore"Anal. Chem.. 73. 939-942 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Kojima, M.Hirata, Y.Kudo, K.Kikuchi, T.Nagano: "Visualization of Oxygen Consumption-dependent Production of Nitric Oxide in Rat Hippocampal Slices during Aglycemia"J. Neurochem.. 76. 1404-1410 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] N.Suzuki, H.Kojima, Y.Urano, K.Kikuchi, Y.Hirata, T.Nagano: "Orthogonality of Calcium Concentration and Ability of 4,5-Diamino fluoresce in (DAF-2) to Detect NO"J. Biol. Chem.. 277. 47-49 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2018-03-28  

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