2001 Fiscal Year Annual Research Report

新機能を有する核酸関連生体分子の人工創製を目指した基礎研究

Research Project

Project/Area Number	11101001
Research Institution	Nagoya University
Principal Investigator	早川芳宏名古屋大学, 大学院・人間情報学研究科, 教授 (50022702)
Co-Investigator(Kenkyū-buntansha)	関根光雄東京工業大学, 大学院・生命理工学研究科, 教授 (40111679) 牧野圭祐京都大学, 国際融合創造センター, 教授 (50159141)
Keywords	ホスホロアミダイト法 / ヌクレオチド化学合成 / CMP-New5Ac / アンチセンス核酸 / デオキシオキザノシン / 2-5A / 一酸化窒素 / テロメア
Research Abstract	早川:ヌクレオシドとヌクレオシドホスホロアミダイトの液相縮合反応おいて、両反応基質および促進剤を化学量論量使用するだけでほぼ定量的に進行させる「モレキュラーシーブス添加ホスホロアミダイト法」を開発した。本法は短鎖ヌクレオチドの液相大量合成にとくに有効で、この方法に基づき、CMP-Neu5Ac、2-5Aコア、c(GpGp)など、重要な天然生体機能物質の高効率合成を達成した。また、アリル保護ホスホロアミダイト法に基づき、デオキシリボヌクレデル化合物である、インターヌクレオチド部のS-アセチルチオエチルトリエステル修飾対の一般高効率合成法を開発した。牧野:ガン抑制遺伝子のCpG site構成成分5mdCydと一酸化窒素の反応でジアゾエート中間体を発見し、ジアゾエート生成による新規G : C→A : T変異を提唱すると共に、全塩基脱アミノ化がジアゾエート中間体を経て起こることを明らかにした。また、本反応において酸素が高濃度で存在すると、デオキシグアノシンから3種類のニトロ化合物が生じることを見出した。さらに一酸化窒素の作用によってデオキシグアノシンから生成するデオキシオキザノシンの細胞内生成検出法、デオキシオキザノシンを含むオリゴDNA合成法を完成した。これ以外に、テロメアのC-repeatとG-repeatのクロストークによる四重鎖構造変化を発見した。関根:H-ホスホネート法による塩基部位無保護DNA合成法における重大な副反応が"5'末端水酸基と最近摂3'リン酸との環化反応に起因する"ことを明らかにし、この知見に基づき活性エステル型改良H-ホスホネート法を開発した。一方、塩基部位をプロトンで保護する"プロトンブロック法"による新規塩基部無保護DNA合成法を開拓した。また、塩基部位がアシル基で保護されたDNAの革新的な合成法を開拓し、このN-アシル型が優れた塩基対形成能をもつことを見出した。

Research Products

(41 results)

All Other

All Publications (41 results)

[Publications] M.Kataoka: "2-Butanoe Peroxide as an Efficient Reagent for the Oxidation of Nucleoside Phosphites into Phosphates under Non-basic, anhydrous Conditions"Org. Lett.. 3. 813-818 (2001)
[Publications] A.Sakakura: "A Facile Synthesis of 5'-End Solid-Anchored, 3'-End Free Oligodeoxyribonucleotides via the (5'→3')-Elongated Phosphoramidite Strategy"Nucleosides Nucleotides Nucleic Acids. 20. 213-227 (2001)
[Publications] Y.Hayakawa: "Nucleotide Synthesis Methods without Nucleoside-Base Protection"Eur. J. Phar. Sci.. 13. 5-16 (2001)
[Publications] Y.Hayakawa: "Acid/Azole Complexes as Highly Effective Promoters in the Synthesis of DNA Oligomers via the Phosphoramidite Method"J. Am. Chem. Soc.. 123. 8165-8176 (2001)
[Publications] N.Spinelli: "Pro-oligonucleotide Synthesis Using Allyl and Allyloxycarbonyl Protections : Direct MALDI-TPF MS Analysis on Solid Support"Nucleosides Nucleotides Nucleic Acids. 20. 947-950 (2001)
[Publications] R.Kawai: "N-Phenylimidazolium Triflate as a Highly Effective Promoter for the Interribonucleotide-Bond Formation via the Phosphoramidite Method"Nucleosides Nucleotides Nucleic Acids. 20. 1047-1048 (2001)
[Publications] Y.Hayakawa: "Toward an Ideal Synthesis of Oligonucleotides : Development of a Novel Phosphoramidite Method with High Capability"Bull. Chem. Soc. Jpn.. 74. 1547-1565 (2001)
[Publications] Y.Hayakawa: "Effect of Molecular Sieves in the Liquid-Phase Synthesis of Nucleotides via the Phosphoamidite Method"Tetrahedron. 57. 8823-8826 (2001)
[Publications] A.Hitara: "Efficient Liquid-Phase Synthesis of Short-Length Nucleotides via the Phosphromidite Method using Stoichiometric Amounts of Reactants"Nucleic Acids Res. Supplement. 1. 215-216 (2001)
[Publications] N.Spinelli: "Use of Allylic Protecting Groups for the Synthesis of Base-Sensitive Prooligonucletides"Eur. J. Org. Chem.. 49-56 (2002)
[Publications] T.Suzuki: "Formation of 2-chloroinosine from guanosine by treatment of HNO2 in the presence of NaCl"Bioorg. Med. Chem.. 9. 2937-2941 (2001)
[Publications] T.Morii: "A general strategy to determine a target DNA sequence of a short peptide : Application to a D-peptide"J. Am. Chem. Soc.. 123. 180-181 (2001)
[Publications] T.Arai: "6-Formylpterin, a xanthine oxidase inhibitor, intracellularly generates reactive oxygen species involved in apoptosis and cell proliferation"Free Rad. Bilo. Med.. 30. 248-259 (2001)
[Publications] N.Endo: "Electrochemical formation of hydrogen atom adduct of 5,5-dimethyl-1-pyrroline-Noxide and its mechanism"Chem. Lett.. 548-549 (2001)
[Publications] M.Hagihara: "Recognition of small molecules by a ribonucleopeptide"Nucleic Acids Res. Supplement. 1. 7-8 (2001)
[Publications] T.Nakano: "Adduct formation between oxanine and amine derivatives"Nucleic Acids Res. Supplement. 1. 47-48 (2001)
[Publications] M.Yamada: "A novel detection method for 2'-deoxyoxanosine"Nucleic Acids Res.Supplement. 1. 159-160 (2001)
[Publications] K.Kanaori: "Effect of complementary C-strand on telomere G-quartet structure"Nucleic Acids Res. Supplement. 1. 265-266 (2001)
[Publications] T.Suzuki: "Formation of a fairy stable diazoate intermediate of 5-methy1-2'-deoxycytidine by HNO2and NO, and its implication to a novel mutatinon mechanism in CpG site"Bioorg. Med. Chem.. 10. 1063-1067 (2002)
[Publications] T.Morii: "Structure-based design of a leucine zipper protein with new DNA contacting region"Biochemistry. 41. 2177-2183 (2002)
[Publications] T.Morii: "A new fluorescent biosensor for inositol triphosphate"J. Am. Chem. Soc.. 124. 1138-1139 (2002)
[Publications] N.Endo: "Electrochemical-ESR detection of hydrogen atom adducts of 5-membered ring nitrone spin traps"Bull. Chem. Soc. Jpn.. 75. 149-150 (2002)
[Publications] H.Terato: "Novel repair activities of AlkA(3-methyladenine DNA glycosylase II) and endonuclease VIII for xanthine and oxanine, guanine lesions induced by nitric oxide and nitrous acid"J. Mol. Biol.. (印刷中).
[Publications] M.Sekine: "Synthesis and Conformational Properties of Dinucleoside Triester Derivative Involving Cyclonucleotide Bridge Structure"Eur. J. Org. Chem.. 1989-1999 (2001)
[Publications] S.Kawahara: "Ab-Initio Evaluation of the Substitution Effect of the Hydrogen-Bond Energy of the Watson-Crick Type Base-Pair Between 1-Mehtyluracil and Substituted 9-Methyladenine Derivatives"J. Phys. Chem.(A). 105. 3894-3898 (2001)
[Publications] M.Kadokura: "Solid-Phase Synthesis of a 5-Terminal TMG-Capped Trinucleotide Block of U1 snRNA"Tetrahedron Lett.. 42. 8853-8856 (2001)
[Publications] M.Sekine: "Total Synthesis of Agrocin 84 and Phosmidosine as Naturally Occurring Nuycleotidic Antibiotics Having P-N Bond Linkages"J. Org. Synth. Chem. Jpn.. 59. 1109-1120 (2001)
[Publications] S.Kawahara: "Ab initio Molecular Orbital Evaluation of the Hydrogen Bond Energy of Base Pairs Formed between Subustituted 1-Mehtylcytosine Derivatives and 9-Mehtylguanine"Nucleic Acids Res. Supplement. 1. 29-30 (2001)
[Publications] A.Ohkubo: "A New Coupling Method for the Synthesis of Oligodeoxyribonucleotides Based on Protection by Protonation of Nuncleoside Bbases"Nucleic Aceds Res. Supplement. 1. 77-78 (2001)
[Publications] K.Sato: "Synthesis and properties of a new nucleotide analogue containing squaryl group"Nucleic Acids Res. Supplement. 1. 121-122 (2001)
[Publications] K.Negishi: "T.Negishi.Binding Specificities of the Mismatch Binding Protein, MutS, to Oligonucleotides Containing Modified Bases"Nucleic Acids Res.Supplement. 1. 221-222 (2001)
[Publications] S.Kawahara: "Theoretical Study of the Hydrogen Bond Energy of Base Paris Formed between Substituted 1-Methylcytosine Derivatives and 9-Methylguanine"J. Phys. Chem.(A). 105. 10596-1061 (2002)
[Publications] K.Seio: "Synthesis of Pentathymidylate Using a 4-Monomethoxytritylthio (MMTrS) Group as a 5'-Hydroxyl Protecting Group : Toward Oligonucleotide Synthesis without Aced Treatment"Tetrahedron Lett.. 42. 8657-8660 (2001)
[Publications] T.Wada: "Synthesis and hybridization Ability of Oligodeoxyribo-nucleotides Incorporating N-Acyldeoxycytidine Derivatives"Eur. J. Org. Chem.. 4583-4593 (2001)
[Publications] Y.Sato: "Substituent and Solvent Effects of TMS-triflate mediated C1'-Epimerization Thymidine"Eur. J. Org. Chem.. 4583-4593 (2001)
[Publications] M.Sekine: "N-Glycosylation"Glycoscience-Chemistry and Chemical biolog I, Reid, B.Fraser, Tatuka, K., Thiem, J.Eds.Medio, Berlin. 673-690
[Publications] T.Wada: "Synthesis and Properties of 2-Azidodeoxyadenosine and Incorporation into Oligodeoxynucleotides"Tetrahedron Lett.. 42. 9215-9219 (2001)
[Publications] A.Kobori: "A New Method for the Synthesis of Oligodeoxynucleotides Containing 4-N-Alkoxycarbonyl deoxycytidine Derivatives and Their Hybridization Property"J. Org. Chem.. 67. 476-485 (2002)
[Publications] A.Kobori: "New Silyl Enther-Type Linker Useful for the Automated Synthesis of Oligonucleotides Having Base-Labile Protection Groups"Chem. Lett.. 16-17 (2002)
[Publications] Y.Sato: "A Convenient Method for the Conversion of β-Thymidine to α-Thymidine Based on TMSOTf-Mediated C1'-Epimerization"Tetrahedron Lett.. (印刷中).
[Publications] T.Moriguchi: "First Synthesis and Anti-Cancer Activity of Phosmidosine and Its Related Compounds"J. Org. Chem.. (印刷中).

2001 Fiscal Year Annual Research Report

新機能を有する核酸関連生体分子の人工創製を目指した基礎研究

Principal Investigator

早川 芳宏 名古屋大学, 大学院・人間情報学研究科, 教授 (50022702)

Research Products

[Publications] M.Kataoka: "2-Butanoe Peroxide as an Efficient Reagent for the Oxidation of Nucleoside Phosphites into Phosphates under Non-basic, anhydrous Conditions"Org. Lett.. 3. 813-818 (2001)

[Publications] A.Sakakura: "A Facile Synthesis of 5'-End Solid-Anchored, 3'-End Free Oligodeoxyribonucleotides via the (5'→3')-Elongated Phosphoramidite Strategy"Nucleosides Nucleotides Nucleic Acids. 20. 213-227 (2001)

[Publications] Y.Hayakawa: "Nucleotide Synthesis Methods without Nucleoside-Base Protection"Eur. J. Phar. Sci.. 13. 5-16 (2001)

[Publications] Y.Hayakawa: "Acid/Azole Complexes as Highly Effective Promoters in the Synthesis of DNA Oligomers via the Phosphoramidite Method"J. Am. Chem. Soc.. 123. 8165-8176 (2001)

[Publications] N.Spinelli: "Pro-oligonucleotide Synthesis Using Allyl and Allyloxycarbonyl Protections : Direct MALDI-TPF MS Analysis on Solid Support"Nucleosides Nucleotides Nucleic Acids. 20. 947-950 (2001)

[Publications] R.Kawai: "N-Phenylimidazolium Triflate as a Highly Effective Promoter for the Interribonucleotide-Bond Formation via the Phosphoramidite Method"Nucleosides Nucleotides Nucleic Acids. 20. 1047-1048 (2001)

[Publications] Y.Hayakawa: "Toward an Ideal Synthesis of Oligonucleotides : Development of a Novel Phosphoramidite Method with High Capability"Bull. Chem. Soc. Jpn.. 74. 1547-1565 (2001)

[Publications] Y.Hayakawa: "Effect of Molecular Sieves in the Liquid-Phase Synthesis of Nucleotides via the Phosphoamidite Method"Tetrahedron. 57. 8823-8826 (2001)

[Publications] A.Hitara: "Efficient Liquid-Phase Synthesis of Short-Length Nucleotides via the Phosphromidite Method using Stoichiometric Amounts of Reactants"Nucleic Acids Res. Supplement. 1. 215-216 (2001)

[Publications] N.Spinelli: "Use of Allylic Protecting Groups for the Synthesis of Base-Sensitive Prooligonucletides"Eur. J. Org. Chem.. 49-56 (2002)

[Publications] T.Suzuki: "Formation of 2-chloroinosine from guanosine by treatment of HNO2 in the presence of NaCl"Bioorg. Med. Chem.. 9. 2937-2941 (2001)

[Publications] T.Morii: "A general strategy to determine a target DNA sequence of a short peptide : Application to a D-peptide"J. Am. Chem. Soc.. 123. 180-181 (2001)

[Publications] T.Arai: "6-Formylpterin, a xanthine oxidase inhibitor, intracellularly generates reactive oxygen species involved in apoptosis and cell proliferation"Free Rad. Bilo. Med.. 30. 248-259 (2001)

[Publications] N.Endo: "Electrochemical formation of hydrogen atom adduct of 5,5-dimethyl-1-pyrroline-Noxide and its mechanism"Chem. Lett.. 548-549 (2001)

[Publications] M.Hagihara: "Recognition of small molecules by a ribonucleopeptide"Nucleic Acids Res. Supplement. 1. 7-8 (2001)

[Publications] T.Nakano: "Adduct formation between oxanine and amine derivatives"Nucleic Acids Res. Supplement. 1. 47-48 (2001)

[Publications] M.Yamada: "A novel detection method for 2'-deoxyoxanosine"Nucleic Acids Res.Supplement. 1. 159-160 (2001)

[Publications] K.Kanaori: "Effect of complementary C-strand on telomere G-quartet structure"Nucleic Acids Res. Supplement. 1. 265-266 (2001)

[Publications] T.Suzuki: "Formation of a fairy stable diazoate intermediate of 5-methy1-2'-deoxycytidine by HNO2and NO, and its implication to a novel mutatinon mechanism in CpG site"Bioorg. Med. Chem.. 10. 1063-1067 (2002)

[Publications] T.Morii: "Structure-based design of a leucine zipper protein with new DNA contacting region"Biochemistry. 41. 2177-2183 (2002)

[Publications] T.Morii: "A new fluorescent biosensor for inositol triphosphate"J. Am. Chem. Soc.. 124. 1138-1139 (2002)

[Publications] N.Endo: "Electrochemical-ESR detection of hydrogen atom adducts of 5-membered ring nitrone spin traps"Bull. Chem. Soc. Jpn.. 75. 149-150 (2002)

[Publications] H.Terato: "Novel repair activities of AlkA(3-methyladenine DNA glycosylase II) and endonuclease VIII for xanthine and oxanine, guanine lesions induced by nitric oxide and nitrous acid"J. Mol. Biol.. (印刷中).

[Publications] M.Sekine: "Synthesis and Conformational Properties of Dinucleoside Triester Derivative Involving Cyclonucleotide Bridge Structure"Eur. J. Org. Chem.. 1989-1999 (2001)

[Publications] S.Kawahara: "Ab-Initio Evaluation of the Substitution Effect of the Hydrogen-Bond Energy of the Watson-Crick Type Base-Pair Between 1-Mehtyluracil and Substituted 9-Methyladenine Derivatives"J. Phys. Chem.(A). 105. 3894-3898 (2001)

[Publications] M.Kadokura: "Solid-Phase Synthesis of a 5-Terminal TMG-Capped Trinucleotide Block of U1 snRNA"Tetrahedron Lett.. 42. 8853-8856 (2001)

[Publications] M.Sekine: "Total Synthesis of Agrocin 84 and Phosmidosine as Naturally Occurring Nuycleotidic Antibiotics Having P-N Bond Linkages"J. Org. Synth. Chem. Jpn.. 59. 1109-1120 (2001)

[Publications] S.Kawahara: "Ab initio Molecular Orbital Evaluation of the Hydrogen Bond Energy of Base Pairs Formed between Subustituted 1-Mehtylcytosine Derivatives and 9-Mehtylguanine"Nucleic Acids Res. Supplement. 1. 29-30 (2001)

[Publications] A.Ohkubo: "A New Coupling Method for the Synthesis of Oligodeoxyribonucleotides Based on Protection by Protonation of Nuncleoside Bbases"Nucleic Aceds Res. Supplement. 1. 77-78 (2001)

[Publications] K.Sato: "Synthesis and properties of a new nucleotide analogue containing squaryl group"Nucleic Acids Res. Supplement. 1. 121-122 (2001)

[Publications] K.Negishi: "T.Negishi.Binding Specificities of the Mismatch Binding Protein, MutS, to Oligonucleotides Containing Modified Bases"Nucleic Acids Res.Supplement. 1. 221-222 (2001)

[Publications] S.Kawahara: "Theoretical Study of the Hydrogen Bond Energy of Base Paris Formed between Substituted 1-Methylcytosine Derivatives and 9-Methylguanine"J. Phys. Chem.(A). 105. 10596-1061 (2002)

[Publications] K.Seio: "Synthesis of Pentathymidylate Using a 4-Monomethoxytritylthio (MMTrS) Group as a 5'-Hydroxyl Protecting Group : Toward Oligonucleotide Synthesis without Aced Treatment"Tetrahedron Lett.. 42. 8657-8660 (2001)

[Publications] T.Wada: "Synthesis and hybridization Ability of Oligodeoxyribo-nucleotides Incorporating N-Acyldeoxycytidine Derivatives"Eur. J. Org. Chem.. 4583-4593 (2001)

[Publications] Y.Sato: "Substituent and Solvent Effects of TMS-triflate mediated C1'-Epimerization Thymidine"Eur. J. Org. Chem.. 4583-4593 (2001)

[Publications] M.Sekine: "N-Glycosylation"Glycoscience-Chemistry and Chemical biolog I, Reid, B.Fraser, Tatuka, K., Thiem, J.Eds.Medio, Berlin. 673-690

[Publications] T.Wada: "Synthesis and Properties of 2-Azidodeoxyadenosine and Incorporation into Oligodeoxynucleotides"Tetrahedron Lett.. 42. 9215-9219 (2001)

[Publications] A.Kobori: "A New Method for the Synthesis of Oligodeoxynucleotides Containing 4-N-Alkoxycarbonyl deoxycytidine Derivatives and Their Hybridization Property"J. Org. Chem.. 67. 476-485 (2002)

[Publications] A.Kobori: "New Silyl Enther-Type Linker Useful for the Automated Synthesis of Oligonucleotides Having Base-Labile Protection Groups"Chem. Lett.. 16-17 (2002)

[Publications] Y.Sato: "A Convenient Method for the Conversion of β-Thymidine to α-Thymidine Based on TMSOTf-Mediated C1'-Epimerization"Tetrahedron Lett.. (印刷中).

[Publications] T.Moriguchi: "First Synthesis and Anti-Cancer Activity of Phosmidosine and Its Related Compounds"J. Org. Chem.. (印刷中).

早川芳宏名古屋大学, 大学院・人間情報学研究科, 教授 (50022702)