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1999 Fiscal Year Final Research Report Summary

SMART MOLECULAR DESIGN OF METAL COMPLEXES WITH BIOLOGICAL ACTIVITIES

Research Project

Project/Area Number 09304061
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Inorganic chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

NAGANO Tetsuo  INSTI, DEPARTMENT, TITLE OF POSITION GRAD SCHOOL PHAR SCI, THE UNIVERSITY OF TOKYO, PROFESSOR, 大学院・薬学系研究科, 教授 (20111552)

Co-Investigator(Kenkyū-buntansha) HIGUCHI Tsunehiko  GRAD SCHOOL PHAR SCI, THE UNIVERSITY OF TOKYO, ASSO. PROF., 大学院・薬学系研究科, 助教授 (50173159)
MASHINO Tadahiko  KYORITSU PHAR COL, ASSO. PROF., 助教授 (90165697)
OHTA Shigeru  SCHOOL MED, HIROSHIMA UNIV, PROFESSOR, 医学部・総合薬学科, 教授 (60160503)
Project Period (FY) 1997 – 1999
Keywordssuperoxide / nitric oxide / zinc / fluorescent probe / reactive oxygen species / bioimaging / nitric oxide synthase / superoxide dismutase
Research Abstract

(1) DEVELOPMENT OF VONEL ZINC FLUORESCENT PROBES EXCITTABLE WITH VISIBLE LIGHT FOR BIOLOGICAL APPLICATIONS
We have developed novel Zn2+ fluorescent probes that are excited by visible light. The probes can selectively detect Zn2+ at physiological pH. The compounds are expected to offer a useful tool for measuring Zn2+ concentration in living cells. Fluorescent probes for Zn2+ have previously been developed. But they are unsuitable for measuring Zn2+ concentration in biological samples in vivo because they either must be excited at ultraviolet wavelengths (which can damage cells) or they operate at a physiologically incompatible alkaline pH. To fashion the new probes we designed and synthesized the fluorophore 6-hydroxy-9-[4-(4, 7, 10-trimethyl-1, 4, 7, 10-tetraazacyclododecan-1-yl)] phenyl-3-one, coupling directly to a macrocyclic ployamine. In various experiments we showed that the fluorescence intensity of both probes increased dramatically as the concentration of Zn2+ is raised. Fluorescence is not affected by high concentrations of Na+, K+, or Mg2+, suggesting that the probes are specific for Zn2+.
(2) DEVELOOPMENT OF NOVEL NIRIC OXIDEFLUORESCENT PROBES
We have highly selective nitric oxide fluorescent probes, which is practically useful for bioimaging.
(3) DEVELOPMENT OF NOVEL Fe COMPLEXES WITH SUPEROXIDE DISMUTASE ACTIVITY AND THEIR APPLICATION
To investigate the relationship between the two structures of Fe-TPEN and superoxide dismutase (SOD), we synthesized novel Fe(II) complexes of TPEN analogues and measures their SOD activity by the cyt. c method. The results show that the substitution reaction of a ligand with superoxide or the coordination of superoxide is essential for Fe(II)TPEN analogue complexes to have SOD activity.

  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Takanari Inoue: "Synthesis and Evaluation of 1 - Postion-modified Inositol 1,4,5-Trisphosphate Analogs"Bioorganic & Medicinal Chemistry Letters. 9. 1697-1702 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Naoki Umezawa: "Novel Jluorescent Probes for Singlet Oxygen"Angewandte Chemie Int. Ed.. 38. 2899-2901 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirotatsu Kojima: "Jluorescent Indicators for Imaging Nitric Oxide Production"Angewandte Chemie Int. Ed.. 38. 3209-3212 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Noriyuki Suguki: "Novel Iron Porphyrin-alkane thiolate Complex with mtramolecular NH… S Hydrogen Bond: tynthesis, Spectrocopy and Reactivity"J.Am . Chem. 80C. 121. 11571-11572 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirotatsu Kojima: "Jluorescent Indicators for Nitric Oxide Based on Rhodamine"Tetrahedron Letters. 41. 69-72 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tetsuo Nagano: "Practical Methods for Detection of Nitric Oxide"Luminescene. 14. 283-290 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小島宏建: "実験医学"羊土社(分担執筆). 946-950 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 長野哲雄: "現代化学"東京化学同人(分担執筆). 23-30 (1999)

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  • [Publications] Kakoki M, Hirata Y, Hayakawa H, Tojo A, Nagata D, Suzuki E, Kimura K, Goto A, Kikuchi K, Nagano T, Omata M,: "Effects of Hypertension, Diabetes Mellitus and Hypercholetsterolemia on Endothelin Type B Receptor-Mediated Nitric Oxide Release From Rat Kidney"Circulation. 99. 1242-1248 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Hayakawa H, Hirata Y, Kakoki M, Suzuki Y, Nishimatsu H, Nagata D, Suzuki E, Kikuchi K, Nagano T, Kanagawa K, Matsuo H, Sugimoto T, Omata M: "Role of Nitric Oxid-cGMP Pathway in Adrenomedullin-induced Vasodilation in the Rat"Hypertension. 33. 689-693 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Kakoki M, Hirata Y, Hayakawa H, Nishimatsu H, Suzuki Y, Nagata D, Suzuki E, Kikuchi K, Nagano T, Omata M: "Effects of Vasodilatory β-Adrenoceptor Antagonists on Endothelium-Derived Nitric Oxide Release in Rat Kidney"Hypertension. 33. 467-471 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Inoue, K. Kikuchi, K. Hirose, M. Iino and T. Nagano: "Synthesis and Evaluation of 1-Position -modified Inositol 1, 4, 5-Trisphosphate Analogs"Bioorganic & Medicinal Chemistry Letter. 9. 1697-1702 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Naoki Umezawa, Kumi Tanaka, Yasuteru Urano, Kazuya Kikuchi, Tsunehiko Higuchi and Tetsuo Nagano: "Novel Fluorescent Probes for Singles Oxygen"Angewandte Chemie Int. ed.. 38. 2899-2901 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shin Mizukami, Kazuya Kikuchi, Tsunehiko Higuchi, Yasuteru Urano, Tetsuo Mashima, Takashi Tsuruo and Tetsuo Nagano: "Imaging of Caspase-3 Activation in HeLa Cells Stimulated with Etoposide Using a Novel Fluorescent Probe"FEBBS Lett.. 453. 356-360 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirotatsu Kojima, Yasuteru Urano, Kazuya Kikuchi, Tsunehiko Higuchi, and Tetsuo Nagano: "Fluorescent Indicators for Imaging Nitric Oxide Production"Angewandte Chemie Int. Ed.. 38. 3209-3212 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Noriyuki Suzuki, Tsunehiko Higuchi, Yasuteru Urano, Kazuya Kikuchi Hidehiko Uekusa, Yuji Ohashi, Takeshi Uchida, Teizoh Kitagawa and Tetsuo Nagano: "Novel Iron Porphyrin-alkanethiolate Complex with Intramolecular NH・・・S Hydrogen Bond : Synthesis, Spectroscopy and Reactivity"J. Am. Chem. Soc.. 121. 11571-11572 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tomoya Hirano, Kazuya Kikuchi, Yasuteru Urano, Tsunehiko Higuchi and Tetsuo Nagano: "Novel zinc fluorescent probe excitable with visible light"Angewandte Chemie Int. Ed.. in press.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tomohisa Hirano, Masaki Hirobe, Kazuo Kobayashi, Akira Odani, Osamu Yamauchi, Masanori Ohsawa, Yoshinori Satow and Tetsuo Nagano: "Mechanism of Superoxide Dismutase Activity of Fe(II) and Fe(III) Complexes of Tetrakis-N, N, N', N' (2-pyridylmethyl) ethylenediamine"Chem. Pharm. Bull.. 48. 223-230 (2000)

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  • [Publications] Masao Kakoki, MD, Yasunobu Hirata, MD, Hiroshi Hayakawa, MD, Etsu Suzuki, MD, Daisuke Nagata, MD, Akihiro Tojo, MD, Hiroaki Nishimatsu, MD, Kazuya Kikuchi, Ph D, Tetsuo Nagano, Ph D, Masao Omata, MD: "Effects of Tetrahydrobiopterin on Endothelial Dysfunction in Rats with Ischemic Acute Renal Failure"J. Am. Soc. Nephrol.. 11. 301-309 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirotatsu Kojima, Miki Hirotani, Yasuteru Urano, Kazuya Kikuchi, Tsunehiko Higuchi and Tetsuo Nagano: "Fluorecent indicators for nitric oxide based on rhodamine chromophore"Tetrahedron Lett.. 41. 69-72 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tetsuo Nagano: "Practical methods for Detection of Nitric Oxide"Luminescence. 14. 283-290 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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