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2005 Fiscal Year Final Research Report Summary

Chemical and Biochemical Studies on Pathological Aspect of Nitric Oxide

Research Project

Project/Area Number 15350099
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemistry related to living body
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

MAKINO Keisuke  Kyoto University, International Innovation Center, Professor, 国際融合創造センター, 教授 (50159141)

Co-Investigator(Kenkyū-buntansha) KODAKI Tsutomu  Kyoto University, Institute ofAdvanced Energy, Associate Professor, エネルギー理工学研究所, 助教授 (70170264)
KANAORI Kenji  Kyoto Institute of Technology, Graduate School of Science and Technology, Associate Professor, 大学院工芸科学研究科, 助教授 (30273543)
Project Period (FY) 2003 – 2005
KeywordsNitric Oxide / Carcinogenesis / Deoxvoxanosine (dOxo) / dOxo amidite monomer synthesis / Synthesis of DNA oligomer containing dOxo / Crosslink formation between dOxo in DNA and repair enzymes / Enzymes repairing dOxo in DNA / Recognition of dOxo in DNA by DNA-relevant enzymes
Research Abstract

Endogenous NO, necessary for many physiological functions, is sometimes overproduced in inflammation and therefore carcinogenic, however no clear evidence has been reported. In this study, we obtained important data to answer this essential question.
1. Oxanine (Oxa), a damaged base generated from Gua by NO-or HNO2-induced nitrosative deamination, has been considered as a mutagen-potent lesion. In this study, for exploring more detailed properties of Oxa, large-scale preparation of Oxa-containing DNA oligomers (Oxa-ODN) was developed: 2'-deoxynucleoside of Oxa (deoxyoxanosine, dOxo) obtained from dGuo by HNO2-nitrosation was subjected to 5'-0-selective tritylation (yield of DMT-dOxo, 70%). Subsequently DMT-dOxo was converted by conventional phosphoramidation to DMT-dOxo-amidite (yield, 72.5%). The amidite was used for synthesizing Oxa-ODNs: The coupling yields for Oxa incorporation and the total synthesis of 25mer DNA were over 93 and 85 %, respectively.
2. Using DNA oligomers with or wi … More thout dOxo as templates and primers, DNA polymerase chain elongation was investigated and we found that in the opposite site to Oxa, T and C are incorporated almost equally, indicating that Oxa is mutagenic.
3. We performed screening for the base-excision repair (BER) system to find no enzymic activity for the excision of Oxa, and revealed that Oxa-polyamine adduct is repaired by the nucleotide excision and recombination repair system, indicative of the cellular Oxa formation and that other DNA-relevant enzymes such as ligase and restriction enzymes recognize Oxa as Gua.
4. We also found that Oxa-recognizing BER enzymes cross-link with Oxa in the DNA duplex irreversibly and this activity is eliminated by heat, while histones binding DNA nonspecifically also crosslink Oxa in DNA duplexes although slowly. This unique crosslinking will be helpful for fishing Oxa-recognizing and-repairing enzymes.
5. NMR analysis for the structure around Oxa in DNA is now being conducted to reveal the mechanism for such unique properties of Oxa. Less

  • Research Products

    (52 results)

All 2006 2005 2004 2003

All Journal Article (40 results) Book (7 results) Patent(Industrial Property Rights) (5 results)

  • [Journal Article] Cloning, expression, and characterization of bacteial L-arabinose l-dehydrogenase involved in an alternative pathway of L-arabinose metabolism.2006

    • Author(s)
      S.Watanabe, T.Kodaki, K.Makino
    • Journal Title

      J. Biol. Chem. 281

      Pages: 2612-2623

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cloning, expression, and characterization of bacterial L-arabinose 1-dehydrogenase involved in an alternative pathway of L-arabinose metabolism2006

    • Author(s)
      S.Watanabe, T.Kodaki, K.Makino
    • Journal Title

      J. Biol. Chem. 281

      Pages: 2612-2623

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Complete reversal of coenzyme specificity of xylitol dehydrogenase and increase of thermostability by the introduction of structural zinc.2005

    • Author(s)
      S.Watanabe, T.Kodaki, K.Makino
    • Journal Title

      J. Biol. Chem. 280

      Pages: 10340-10349

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Repair activity of base and nucleotide excision repair enzymes for guanine lesions induced by nitrosative stress.2005

    • Author(s)
      T.Nakano, A.Katafuchi, R.Shimizu, H.Terato, T.Suzuki, H.Tauchi, K.Makino, M.Skorvaga, B.Van Houten, H.Ide
    • Journal Title

      Nucleic Acids Res. 33

      Pages: 2181-2191

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Protective effects of intracellular reactive oxygen species generated by 6-formylpterin on tumor necrosis factor-α-induced apoptotic cell injury in cultured rat hepatocytes.2005

    • Author(s)
      H.Ishii, T.Arai, H.Mori, H.Yamada, N.Endo, K.Makino, K.Fukuda
    • Journal Title

      Life Sci. 77

      Pages: 858-868

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A navel method for synthesis of silica nanoparticles.2005

    • Author(s)
      S.R.Kota, E.-H.Khalil, T.Kodaki, K.Matsushige, K.Makino
    • Journal Title

      J. Colloid and Interface Sci. 289

      Pages: 125-131

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Photodynamic effects of a novel pterin derivative on a pancreatic cancer cell line.2005

    • Author(s)
      H.Yamada, T.Arai, N.Endo, K.Yamashita, M.Nonogawa, K.Makino, K.Fukuda, M.Sasada, T.Uchiyama
    • Journal Title

      Biochem. Biophys. Res. Commn. 333

      Pages: 763-767

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Chemical synthesis and thermodynamic characterization of oxanine-containing oligodeoxynucleotides.2005

    • Author(s)
      S.P.Pack, M.Nonogawa, T.Kodaki, K.Makino
    • Journal Title

      Nucleic Acid Res 33

      Pages: 5771-5780

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A hydrogen peroxide-generating agent, 6-formylpterin, enchances heat-induced apoptosis.2005

    • Author(s)
      S.Wada, Z.-G.Cui, T.Kondo, Q.-L.Zhao, R.Ogawa, M.Shoji, T.Arai, K.Makino, I.Furuta
    • Journal Title

      Int. J. Hyprethermia 21

      Pages: 231-246

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Electron spin resonance analysis of the oxidation reactions of nitrone type spin traps with gold(III) ion.2005

    • Author(s)
      A.Nakajima, Y.Ueda, N.Endo, K.Tajima, K.Makino
    • Journal Title

      Can. J. Chem. 83

      Pages: 1178-1184

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Biophysical and biochemical properties of oxanine-containing oligodeoxynucleotide.2005

    • Author(s)
      S.P.Pack, M.Nonogawa, N.K.Kamisetty, T.Kodaki, K.Makino
    • Journal Title

      Nucleic Acids Symp. Ser. 49

      Pages: 95-96

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Fabrication of effecient DNA microarray by additional surface modification and functional probe design.2005

    • Author(s)
      N.K.Kamisetty, S.P.Pack, M.Nonogawa, T.Kodaki, K.Makino
    • Journal Title

      Nucleic Acids Symp. Ser. 49

      Pages: 225-226

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] L-Arabinose l-dehydrogenase : a novel enzyme involving in bacterial L-arabinose metabolism.2005

    • Author(s)
      S.Watanabe, T.Kodaki, K.Makino
    • Journal Title

      Nucleic Acids Symp. Ser. 49

      Pages: 309-310

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Hydrogen bond removal of pterin derivative whose structure is similar to nucleic acid bases.2005

    • Author(s)
      M.Nonogawa, T.Arai, N.Endo, S.P.Pack, T.Kodaki, K.Makino
    • Journal Title

      Nucleic Acids Symp. Ser. 49

      Pages: 311-312

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Protective effects of intracellular reactive oxygen species generated by 6-formylpterin on tumor necrosis factor-a-induced apoptotic cell injury in cultured rat hepatocytes.2005

    • Author(s)
      H.Ishii, T.Arai, H.Mori, H.Yamada, N.Endo, K.Makino, K.Fukuda
    • Journal Title

      Life Sci. 77

      Pages: 858-868

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A novel method for synthesis of silica nanoparticles.2005

    • Author(s)
      S.R.Kota, E.-H.Khalil, T.Kodaki, K.Matsushige, K.Makino
    • Journal Title

      J. Colloid and Interface Sci. 289

      Pages: 125-131

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Chemical synthesis and thermodynamic characterization of oxanine-containing oligodeoxynucleotides.2005

    • Author(s)
      S.P.Pack, M.Nonogawa, T.Kodaki, K.Makino
    • Journal Title

      Nucleic Acid Res. 33

      Pages: 5771-5780

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A hydrogen peroxide-generating agent, 6-formylpterin, enhances heat-induced apoptosis.2005

    • Author(s)
      S.Wada, Z.-G.Cui, T.Kondo, Q.-L.Zhao, R.Ogawa, M.Shoji, T.Arai, K.Makino, I.Furuta
    • Journal Title

      Int. J. Hyprethermia 21

      Pages: 231-246

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Fabrication of efficient DNA microarray by additional surface modification and functional probe design.2005

    • Author(s)
      N.K.Kamisetty, S.P.Pack, M.Nonogawa, T.Kodaki, K.Makino
    • Journal Title

      Nucleic Acids Symp. Ser. 49

      Pages: 225-226

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] L-Arabinose 1-dehydrogenase : a novel enzyme involving in bacterial L-arabinose metabolism.2005

    • Author(s)
      S.Watanabe, T.Kodaki, K.Makino
    • Journal Title

      Nucleic Acids Symp. Ser. 49

      Pages: 309-310

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effects of intracellular reactive oxygen species generated by 6-formylpterin on T cell functions.2004

    • Author(s)
      T.Arai, H.Yamada, T.Namba, H.Mori, H.Ishii, K.Yamashita, M.Sasada, K.Makino, K.Fukuda
    • Journal Title

      Biochem. Pharmacol. 67

      Pages: 1185-1193

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effect of phosphorothioate chirality on i-motif structure and stability.2004

    • Author(s)
      K.Kanaori, S.Sakamoto, H.Yoshida, P.Guga, W.Stec, K.Tajima, K.Makino
    • Journal Title

      Biochemistry 43

      Pages: 5672-5679

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Enhancement of radiation-induced apoptosis by 6-formylpterin.2004

    • Author(s)
      Z.-G.Cui, T.Kondo, R.Ogawa, L.B.Feril, Q.-L.Zhao, S.Wada, T.Arai, K.Makino
    • Journal Title

      Free Radical Res. 38

      Pages: 363-373

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Novel real-time sensors to quantitatively assess in vivo inositol 1,4,5-trisphosphate production in intact cells.2004

    • Author(s)
      K.Sugimoto, M.Nishida, M.Otsuka, K.Makino, K.Ohkubo, Y.Mori, T.Morii
    • Journal Title

      Chem. Biol. 11

      Pages: 475-485

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Various Mutations by Using Yeast Gene for Protein-Engineering.2004

    • Author(s)
      S.Watanabe, T.Kodaki, K.Makino
    • Journal Title

      Nucleic Acids Symp. Ser. 48

      Pages: 197-198

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] ^1H NMR Study on equilibrium between pararell G-quartet structures.2004

    • Author(s)
      K.Kanaori, A.Yasumura, K.Tajima, K.Makino
    • Journal Title

      Nucleic Acids Symp. Ser. 48

      Pages: 233-234

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Chemical Synthesis of Oxanine-Contained Oligodeoxynucleotides.2004

    • Author(s)
      S.P.Pack, D.Yamamoto, T.Kodaki, K.Makino
    • Journal Title

      Nucleic Acids Symp. Ser. 48

      Pages: 249-250

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effects of intracellular reactive oxygen species generated by 6-formylpterin on T cell functions.2004

    • Author(s)
      T.Arai, H.Yamada, T.Namba, H.Mori, H.Ishii, K.Yamashita, M.Sasada, K.Makino, K.Fukuda
    • Journal Title

      Biochemical Pharmacology 67

      Pages: 1185-1193

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] ^lH NMR Study on equilibrium between pararell G-quartet structures.2004

    • Author(s)
      K.Kanaori, A.Yasumura, K.Tajima, K.Makino
    • Journal Title

      Nucleic Acids Symp. Ser. 48

      Pages: 233-234

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effects of 6-formylpterin as an internal source of hydrogen peroxideon cell death of human peripheral blood leukocytes.2003

    • Author(s)
      M.Nishioka, T.Arai, K.Yamashita, M.Sasada, H.Morii, H.Ishii, K.Tajima, K.Makino, K.Fukuda
    • Journal Title

      Life Sci. 73

      Pages: 221-231

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Functional reassembly of a split PH domain.2003

    • Author(s)
      K.Sugimoto, Y.Mori, K.Makino, K.Ohkubo, T.Morii
    • Journal Title

      J. Am. Chem. Soc. 125

      Pages: 5000-5004

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Nitration of 2'-deoxyguanosine by a <NO/O_2> gas mixture : Identification and characterization of <N^2-nitro-2'-deoxyguanosine>.2003

    • Author(s)
      M.Yamada, T.Suzuki, K.Kanaori, K.Tajima, S.Sakamoto, T.Kodaki, K.Makino
    • Journal Title

      Org. Lett. 5

      Pages: 3173-3176

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 6-Formylpterin protects retinal neurona from transient ischemia-reperfusion injury in rats : A morphological and immunohistochemical study.2003

    • Author(s)
      T.Funakoshi, H.Miyata, T.Imoto, T.Arai, N.Endo, K.Makino, C.H.Yang, E.Ohama
    • Journal Title

      Neuropathology 23

      Pages: 161-168

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] DNA-protein cross-link formation mediated by oxanine. A novel genotoxic mechanism of nitric oxide-induced DNA damage.2003

    • Author(s)
      T.Nakano, H.Terato, K.Asagoshi, A.Masaoka, M.Mukuta, Y.Ohyama, T.Suzuki, K.Makino, H.Ide
    • Journal Title

      J. Biol. Chem. 278

      Pages: 25264-25272

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Differential transcriptional regulation of two distinct S-adenosylmethionine synthetase genes (SAM1 and SAM2) of Saccharomyces serevisiae.2003

    • Author(s)
      T.Kodaki, S.Tsuji, N.Otani, D.Yamamoto, K.S.Rao, S.Watanabe, M.Tsukatsune, K.Makino
    • Journal Title

      Nucleic Acids Res. Supplement 3

      Pages: 303-304

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effects of 6-formylpterin as an internal source of hydrogen peroxide on cell death of human peripheral blood leukocytes.2003

    • Author(s)
      M.Nishioka, T.Arai, K.Yamashita, M.Sasada, H.Morii, H.Ishii, K.Tajima, K.Makino, K.Fukuda
    • Journal Title

      Life Sci. 73

      Pages: 221-231

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Functional reassembly of a split PH domain.2003

    • Author(s)
      K.Sugimoto, Y.Mori, K.Makino, K.Ohkubo, T.Morii
    • Journal Title

      J.Am.Chem.Soc. 125

      Pages: 5000-5004

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Nitration of 2'-deoxyguanosine by a NO/O2 gas mixture : Identification and characterization of N2-nitro-2'-deoxyguanosine.2003

    • Author(s)
      M.Yamada, T.Suzuki, K.Kanaori, K.Tajima, S.Sakamoto, T.Kodaki, K.Makino
    • Journal Title

      Org. Lett. 5

      Pages: 3173-3176

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Formylpterin protects retinal neurons from transient ischemia-reperfusion injury in rats : A morphological and immunohistochemical study.2003

    • Author(s)
      T.Funakoshi, H.Miyata, T.Imoto, T.Arai, N.Endo, K.Makino, C.H.Yang, E.Ohama
    • Journal Title

      Neuropathology 23

      Pages: 161-168

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Differential transcriptional regulation of two distinct S-adenosylmethionine synthetase genes (SAMI and SAM2) of Saccharomyces serevisiae.2003

    • Author(s)
      T.Kodaki, S.Tsuji, N.Otani, D.Yamamoto, K.S.Rao, S.Watanabe, M.Tsukatsune, K.Makino
    • Journal Title

      Nucleic Acids Res. Supplement 3

      Pages: 303-304

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 「DNA マイクロアレイ」(「生物薬科学実験講座」 第2巻 核酸 [I] 核酸の合成と分析、第2章核酸の分析)(杉浦幸雄編集)2005

    • Author(s)
      牧野 圭祐, 金原 秀行
    • Total Pages
      20
    • Publisher
      廣川書店
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Reaction of NO with Nucleic Acid Bases and Its Biological Implication in "Genomic Chemistry (Ed. Y. Hayakawa)"2005

    • Author(s)
      S.P.Pack, T.Suzuki, H.Ide, T.Kodaki, K.Makino
    • Total Pages
      44
    • Publisher
      Bentham Science Publisher Ltd., USA
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] DNA マイクロアレイの構造と開発技術2005

    • Author(s)
      牧野 圭祐
    • Total Pages
      7
    • Publisher
      技術情報協会(MATERIAL STAGE, vol.4)
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 終わりに-未来を拓く電子スピンサイエンス(「電子スピンサイエンス&スピンテクノロジー入門」)(電子スピンサイエンス学会監)2004

    • Author(s)
      牧野 圭祐
    • Total Pages
      6
    • Publisher
      日本学会事務センター
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 第6章 環境ホルモンの科学(「京大人気講義シリーズ エネルギー・環境・社会 現代技術社会論」)(京都大学大学院エネルギー科学研究科エネルギー社会・環境科学専攻編)2004

    • Author(s)
      牧野 圭祐
    • Total Pages
      17
    • Publisher
      丸善
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] バイオマスのエタノール変換-プロテイン工学的アプローチ2004

    • Author(s)
      小瀧 努, 渡邉 誠也, 牧野 圭祐
    • Total Pages
      16
    • Publisher
      シーエムシー出版(月刊エコインダストリー、Vol 9)
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] DNA-金コンジュゲート(「ゲノムケミストリー」)(関根光男、齋藤烈編)2003

    • Author(s)
      牧野 圭祐, 金原 秀行
    • Total Pages
      24
    • Publisher
      講談社サイエンティフィク
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] リンカー用化合物、プローブ及びプローブ固定化担体2006

    • Inventor(s)
      牧野圭祐, 小瀧努, 渡邉誠也, スンピル・パック, 野々川満, 和田啓男, 吉田安子, 山田和成
    • Industrial Property Rights Holder
      国立大学法人京都大学, 日本碍子, 信和化丁.
    • Industrial Property Number
      PCT/JP2006/304641
    • Filing Date
      2006-03-09
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] リンカー用化合物、プローブ及びプローブ固定化担体2006

    • Inventor(s)
      牧野圭祐, 吉田安子, 山田和成
    • Industrial Property Rights Holder
      国立大学法人京都大学
    • Industrial Property Number
      PCT/JP2006/304642
    • Filing Date
      2006-03-09
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] リンカー化合物、プローブ及びプローブ固定化担体2005

    • Inventor(s)
      牧野圭祐, 小瀧努, 渡邉誠也, スンピル・パック, 野々川満, 和田啓男, 吉田安子, 山田和成
    • Industrial Property Rights Holder
      国立大学法人京都大学, 日本碍子, 信和化丁.
    • Industrial Property Number
      特願2005-065948
    • Filing Date
      2005-03-09
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] L-アラビノースをα-ケトグルタル酸に変換する方法、この方法に使用する酵素、該酵素をコードする遺伝子、該遺伝子を含む組換え微生物2005

    • Inventor(s)
      牧野圭祐, 小瀧努, 渡邉誠也, 和田啓男
    • Industrial Property Rights Holder
      国立大学法人京都大学, 信和化丁.
    • Industrial Property Number
      特願2005-303253
    • Filing Date
      2005-10-18
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 変異型キシリトールデヒドロゲナーゼ酵素、これを生産する微生物、該酵素または微生物を用いたキシリトールをキシロースに変換する方法2004

    • Inventor(s)
      牧野圭祐, 小瀧努, 渡邉誠也, 和田啓男
    • Industrial Property Rights Holder
      国立大学法人京都大学, 信和化丁.
    • Industrial Property Number
      特願2004-188417
    • Filing Date
      2004-06-25
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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