2000 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・生命理工学研究所, 教授 (40111679) 牧野圭祐京都大学, エネルギー理工学研究所, 教授 (50159141)
Keywords	RNAオリゴマー / 酸 / アゾール複合体 / 一酸化窒素 / 遺伝子傷害 / クロスリンク / N-アシルDNA / 塩基対形成能 / 分子認識能
Research Abstract	早川:原料として反応性の低いアミダイトを用いるRNAオリゴマーおよびリン酸部修飾機能性DNAオリゴマーの高効率合成に有効な、高い活性をもつ種々の酸/アゾール複合型促進剤を開発した。なかでもとくに高い反応性をもつN-フェニルイミダゾール/トリフルオロメタンスルホン酸複合体を促進剤に用いるホスホロアミダイト法により、従来法に比べはるかに効率が良く、再現性に優れるRNAオリゴマーの液相、固相合成法を開発した。また重要な機能性核酸関連物質であるCMP-5NeuAcや2-5Aコアなどの新規高効率合成を達成した。牧野:化学合成したオキザノシンを含むオリゴヌクレオチドをテンプレートとして用い、DNA複製によってこれらの損傷塩基の催奇性への影響を明らかにした。また、オキザノシンを含むオリゴヌクレオチドとヒストンに含まれるアミノ酸であるリジンとの反応を解析し、オギザノシンが効率よくリジン付加体を生成することを明らかにした。関根:塩基部位が保護された人工DNAオリゴマーのRNAを中心とする生体分子の分子認識能の研究を開始し・まず新規リンカーを開発することによってシトシン塩基に様々なアシル基が導入されたDNAオリゴマーの高効率合成を達成した。ついでこの人工DNAオリゴマーのmRNAへの結合能を検討し、N-アシルデオキシシチジンとしてN-(4-メトキシブチリル)-あるいはN-カルバモイルデオキシシチジンを含むオリゴマーが塩基対形成能および分子識別能の点で優れた性質をもつことを見出した。

Research Products

(36 results)

All Other

All Publications (36 results)

[Publications] Sakakura,A.: "A Novel Synthesis of Oligonucleotide-Peptide Conjugates with a Base-Labile Phosphate Linker between the Two Components According to the Allyl-Protected Phosphoramidite Strategy"Tetrrahedron. 56. 4427-4435 (2000)
[Publications] Matsuura,K.: "Phosphoramidite Solid-Phase Synthesis of Site-Specifically Glycosylated Oligodeoxynuleotides"Tetrahedron Lett.. 41. 7529-7533 (2000)
[Publications] Sakakura,A.: "An Efficient Synthesis of Nucleotides via the Phosphoramidite Method Using a Triflic Acid Salt of Imidazole-Related Compound as a Promoter"Nucleic Acids Symp.Ser.. 44. 137-138 (2000)
[Publications] Sakakura,A.: "A Facile Synthesis of 5'-End Solid-Anchored, 3'-End Free Oligodeoxyribonucleotides via the (5'-3')-Elongated Phosphoramidite Strategy"Nucleosides Nucleotides Nucleic Acids. 20(in press).
[Publications] Hayakawa,Y.: "Nucleotide Synthesis via Methods without Nucleoside-Base Protection"Eur.J.Pharm.Sci.. (in press).
[Publications] Kawai,R.: "N-Phenylimidazolium Triflate as a Highly Effective Promoter for the Interribonucleotide-Bond Formation via the Phosphoramidite Method"Nucleosides Nucleotides Nucleic Acids. 20(in press).
[Publications] Kataoka,M.: "Ethyl (methyl) dioxirane as an Efficient Reagent for the Oxidation of Nucleoside Phosphites into Phosphates under Non-basic, Anhydrous Conditions"Org.Lett.. 3(in press).
[Publications] Suzuki,T.: "Formation of 2'-deoxyoxanosine from 2'--deoxyguanosine and nitrous acid : Mechanism and intermediates"Nucleic Acids Res.. 28. 544-551 (2000)
[Publications] Suzuki,T.: "Identification and characterization of a reaction product of 2'-deoxyoxanosine with glycine"Chem.Res.Toxicol.. 13. 227-230 (2000)
[Publications] Suzuki,T.: "Influence of ring opening-closure equilibrium of oxanine, a novel damaged nucleobase, on migration behavior in capillary electrophoresis"J.Chromatogr.A. 877. 225-232 (2000)
[Publications] Suzuki,T.: "Products of the reaction between a diazoate derivative of 2'-deoxycytidine and L-lysine and its implication for DNA-nucleoprotein cross-linking by NO or HNO_2"Chem.Res.Toxicol.. 13. 1223-1227 (2000)
[Publications] Sato,S.: "DNA binding of a basic leucine-zipper protein with novel folding domain"Nucleic Acids Res.Symp.Ser.. 44. 13-14 (2000)
[Publications] Yamada,M.: "NO induced novel DNA lesions : Formation mechanism"Nucleic Acids Res.Symp.Ser.. 44. 273-274 (2000)
[Publications] Seio,K.: "Synthesis and Properties of Oligodeoxythymidylates Incorporating an Artificial Bend Motif"Helv.Chim.Acta. 83. 162-180 (2000)
[Publications] Matsuo,H.: "Efficient Synthesis of ^<13>C, ^<15>N-Labeled RNA Containing the Cap Structure m^7GpppA"J.Am.Chem.Soc.. 122. 2417-2421 (2000)
[Publications] Moriguchi,T.: "Synthesis and Antitumor Activities of Phosmidosine A and Its N-Acylated Derivative"Tetrahedron Lett.. 41. 5881-5885 (2000)
[Publications] Sekine,M.: "Synthesis and Properties of Oligodeoxynucleotides Incorporating a Conformationally Ridid uridine Unit having a Cyclic Structure at the 5'-Terminal Site"J.Org.Chm.. 65. 3571-3578 (2000)
[Publications] Shohda,K.: "Synthesis and Properties of 2'-O-Methyl-2-thiouridine and Oligoribonucleotides Containing 2'-O-Methyl-2-thiouridine"Bioorg.Med.Chem.Lett.. 10. 1795-1798 (2000)
[Publications] Tsuruoka,H.: "Synthesis and Conformational Properties of Oligonucleotides Incorporating 2'-O-phosphorylated Ribonucleotide as Structural Motifs of Pre-tRNA Splicing Intermediates"J.Org.Chem.. 65. 7479-7494 (2000)
[Publications] Kadokura,M.: "Synthesis of 4-Thiouridine, 6-Thioinosine and 6-Thioguanosine 3'5'-O-Bisphosphates as Donor Molecules for RNA Ligation and Their Application to the Synthesis of Photoactivatable TMG-Capped U1 RNA Fragments"J.Org.Chem.. 65. 5104-5113 (2000)
[Publications] Sekine,M.: "Synthesis and Properties of Oligonucleotides Having a Phosphorus Chiral Center by Incorporation of Conformationally Rigid 5'-Cyclouridylic Acid Derivatives"J.Org.Chem.. 65. 6515-6524 (2000)
[Publications] Narita,H.: "Synthesis of N-Labeled Peptidyl AMP"Nucleosides Nucleotides Nucleic Acids. (in press).
[Publications] Moriguchi,T.: "Synthesis and Properties of Aminoacylamido-AMP : Chemical Optimization for the Construction of an N-Acyl Phosphoramidate Linkage"J.Org.Chem.. 65. 8229-8238 (2000)
[Publications] Kawahara,S.: "Evaluation of the Hydrogen Bond Energy of Base Pairs Formed between Substituted 9-Methyladenine Derivatives and 1-Methyluracil by Use of Molecular Orbital theory"Nucleic Acids Symposium Ser.. 44. 237-238 (2000)
[Publications] Ushioda,K.: "Solid-Phase Synthesis of Deoxyribonucleotides Having a Cap Structure Analogue"Nuceic Acids Symposium Ser.. 44. 123-124 (2000)
[Publications] Y.Satoh,Y.: "Chemical Synthesis of Hydroxymethylphosphonate α-DNA"Nuceic Acids Symposium Ser.. 44. 131-132 (2000)
[Publications] S.Kawahara,S.: "The Hydrogen Bond Energy on Mismatched Base Pair Formation between Uracil Derivatives and Guanine in the Gas Phase and in the Aqueous Pphase"J.Mol.Struct.(THEOCHEM). 530. 109-117 (2000)
[Publications] Wada,T.: "2-(Azidomethyl) benzoyl as a new protecting group in nucleosides"Tetrahedron Lett.. (in press).
[Publications] Sekine,M.: "Synthesis and Conformational Properties of Dinucleoside Triester Derivatives Involving a Cyclonucleotide Bridge Structure"Eur.J.Org.Chem.. (in press).
[Publications] Kawahara,S.: "The Hyudrogen Bond Energy of the Watson-Crick type Base Pair between Uracil and Substituted Adenine Derivatives : Ab initio Evaluation of the Substitution Effects"J.Phys.Chem.(A). (in press).
[Publications] Mori,H.: "Effects of 6-formylpterin, a xanthine oxidase inhibitor and a superoxide scavenger on production of nitric oxide in RAW 264.7 macropharges"Biochim.Biophys.Acta. 1474. 93-99 (2000)
[Publications] Masaoka,H.: "Preparation and enzymatic recognition of guanine lesions induced by nitrogen oxide"Nucleic Acids Symp.Ser.. 44. 87-88 (2000)
[Publications] Arai,T.: "6-Formylpterin, a xanthine oxidase inhibitor, intracellularly generates reactive oxygen species involved in apoptosis and cell proliferation"Free Rad.Biol.Med.. 30. 248-259 (2001)
[Publications] 牧野圭祐: "一酸化窒素の生化学"化学と生物. 38. 14-19 (2000)
[Publications] 牧野圭祐: "アイピーシー"バイオマスからの環境ホルモン(坂志朗編「バイオマス・エネルギー・環境」)(印刷中).
[Publications] 牧野圭祐編: "廣川書店"超臨界クロマトグラフィー("Supercritical Fluid Chromatography",Ed.R.M.Smith,Royal Society of Chemistry,London)(印刷中).

2000 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] Sakakura,A.: "A Novel Synthesis of Oligonucleotide-Peptide Conjugates with a Base-Labile Phosphate Linker between the Two Components According to the Allyl-Protected Phosphoramidite Strategy"Tetrrahedron. 56. 4427-4435 (2000)

[Publications] Matsuura,K.: "Phosphoramidite Solid-Phase Synthesis of Site-Specifically Glycosylated Oligodeoxynuleotides"Tetrahedron Lett.. 41. 7529-7533 (2000)

[Publications] Sakakura,A.: "An Efficient Synthesis of Nucleotides via the Phosphoramidite Method Using a Triflic Acid Salt of Imidazole-Related Compound as a Promoter"Nucleic Acids Symp.Ser.. 44. 137-138 (2000)

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

[Publications] Hayakawa,Y.: "Nucleotide Synthesis via Methods without Nucleoside-Base Protection"Eur.J.Pharm.Sci.. (in press).

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

[Publications] Kataoka,M.: "Ethyl (methyl) dioxirane as an Efficient Reagent for the Oxidation of Nucleoside Phosphites into Phosphates under Non-basic, Anhydrous Conditions"Org.Lett.. 3(in press).

[Publications] Suzuki,T.: "Formation of 2'-deoxyoxanosine from 2'--deoxyguanosine and nitrous acid : Mechanism and intermediates"Nucleic Acids Res.. 28. 544-551 (2000)

[Publications] Suzuki,T.: "Identification and characterization of a reaction product of 2'-deoxyoxanosine with glycine"Chem.Res.Toxicol.. 13. 227-230 (2000)

[Publications] Suzuki,T.: "Influence of ring opening-closure equilibrium of oxanine, a novel damaged nucleobase, on migration behavior in capillary electrophoresis"J.Chromatogr.A. 877. 225-232 (2000)

[Publications] Suzuki,T.: "Products of the reaction between a diazoate derivative of 2'-deoxycytidine and L-lysine and its implication for DNA-nucleoprotein cross-linking by NO or HNO_2"Chem.Res.Toxicol.. 13. 1223-1227 (2000)

[Publications] Sato,S.: "DNA binding of a basic leucine-zipper protein with novel folding domain"Nucleic Acids Res.Symp.Ser.. 44. 13-14 (2000)

[Publications] Yamada,M.: "NO induced novel DNA lesions : Formation mechanism"Nucleic Acids Res.Symp.Ser.. 44. 273-274 (2000)

[Publications] Seio,K.: "Synthesis and Properties of Oligodeoxythymidylates Incorporating an Artificial Bend Motif"Helv.Chim.Acta. 83. 162-180 (2000)

[Publications] Matsuo,H.: "Efficient Synthesis of ^<13>C, ^<15>N-Labeled RNA Containing the Cap Structure m^7GpppA"J.Am.Chem.Soc.. 122. 2417-2421 (2000)

[Publications] Moriguchi,T.: "Synthesis and Antitumor Activities of Phosmidosine A and Its N-Acylated Derivative"Tetrahedron Lett.. 41. 5881-5885 (2000)

[Publications] Sekine,M.: "Synthesis and Properties of Oligodeoxynucleotides Incorporating a Conformationally Ridid uridine Unit having a Cyclic Structure at the 5'-Terminal Site"J.Org.Chm.. 65. 3571-3578 (2000)

[Publications] Shohda,K.: "Synthesis and Properties of 2'-O-Methyl-2-thiouridine and Oligoribonucleotides Containing 2'-O-Methyl-2-thiouridine"Bioorg.Med.Chem.Lett.. 10. 1795-1798 (2000)

[Publications] Tsuruoka,H.: "Synthesis and Conformational Properties of Oligonucleotides Incorporating 2'-O-phosphorylated Ribonucleotide as Structural Motifs of Pre-tRNA Splicing Intermediates"J.Org.Chem.. 65. 7479-7494 (2000)

[Publications] Kadokura,M.: "Synthesis of 4-Thiouridine, 6-Thioinosine and 6-Thioguanosine 3'5'-O-Bisphosphates as Donor Molecules for RNA Ligation and Their Application to the Synthesis of Photoactivatable TMG-Capped U1 RNA Fragments"J.Org.Chem.. 65. 5104-5113 (2000)

[Publications] Sekine,M.: "Synthesis and Properties of Oligonucleotides Having a Phosphorus Chiral Center by Incorporation of Conformationally Rigid 5'-Cyclouridylic Acid Derivatives"J.Org.Chem.. 65. 6515-6524 (2000)

[Publications] Narita,H.: "Synthesis of N-Labeled Peptidyl AMP"Nucleosides Nucleotides Nucleic Acids. (in press).

[Publications] Moriguchi,T.: "Synthesis and Properties of Aminoacylamido-AMP : Chemical Optimization for the Construction of an N-Acyl Phosphoramidate Linkage"J.Org.Chem.. 65. 8229-8238 (2000)

[Publications] Kawahara,S.: "Evaluation of the Hydrogen Bond Energy of Base Pairs Formed between Substituted 9-Methyladenine Derivatives and 1-Methyluracil by Use of Molecular Orbital theory"Nucleic Acids Symposium Ser.. 44. 237-238 (2000)

[Publications] Ushioda,K.: "Solid-Phase Synthesis of Deoxyribonucleotides Having a Cap Structure Analogue"Nuceic Acids Symposium Ser.. 44. 123-124 (2000)

[Publications] Y.Satoh,Y.: "Chemical Synthesis of Hydroxymethylphosphonate α-DNA"Nuceic Acids Symposium Ser.. 44. 131-132 (2000)

[Publications] S.Kawahara,S.: "The Hydrogen Bond Energy on Mismatched Base Pair Formation between Uracil Derivatives and Guanine in the Gas Phase and in the Aqueous Pphase"J.Mol.Struct.(THEOCHEM). 530. 109-117 (2000)

[Publications] Wada,T.: "2-(Azidomethyl) benzoyl as a new protecting group in nucleosides"Tetrahedron Lett.. (in press).

[Publications] Sekine,M.: "Synthesis and Conformational Properties of Dinucleoside Triester Derivatives Involving a Cyclonucleotide Bridge Structure"Eur.J.Org.Chem.. (in press).

[Publications] Kawahara,S.: "The Hyudrogen Bond Energy of the Watson-Crick type Base Pair between Uracil and Substituted Adenine Derivatives : Ab initio Evaluation of the Substitution Effects"J.Phys.Chem.(A). (in press).

[Publications] Mori,H.: "Effects of 6-formylpterin, a xanthine oxidase inhibitor and a superoxide scavenger on production of nitric oxide in RAW 264.7 macropharges"Biochim.Biophys.Acta. 1474. 93-99 (2000)

[Publications] Masaoka,H.: "Preparation and enzymatic recognition of guanine lesions induced by nitrogen oxide"Nucleic Acids Symp.Ser.. 44. 87-88 (2000)

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

[Publications] 牧野圭祐: "一酸化窒素の生化学"化学と生物. 38. 14-19 (2000)

[Publications] 牧野圭祐: "アイピーシー"バイオマスからの環境ホルモン(坂志朗編「バイオマス・エネルギー・環境」)(印刷中).

[Publications] 牧野圭祐編: "廣川書店"超臨界クロマトグラフィー("Supercritical Fluid Chromatography",Ed.R.M.Smith,Royal Society of Chemistry,London)(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)