1992 年度実績報告書

特異な構造をもつRNAの化学合成と反応

研究課題

研究課題/領域番号	04226105
研究機関	名古屋大学
研究代表者	早川芳宏名古屋大学, 大学院人間情報学研究科, 教授 (50022702)
研究分担者	沢井宏明群馬大学, 工学部, 教授 (70012648) 石戸良治東京薬科大学, 薬学部, 教授 (60016037) 清水剛夫京都大学, 工学部, 教授 (10025893) 畑辻明東京工業大学, 大学院総合理工学研究科, 教授 (00016049)
キーワード	人工制限酵素 / リン酸トリエステル修飾DNA / キャップ構造 / オリゴヌクレオチド / ヌクレオチドリンポルフィリン誘導体 / オリゴチオアデニル酸 / アンチセンス核酸 / 2-5A
研究概要	位置特異的にDNAを加水分解的に切断する機能、すなわち制限酵素機能を有する人工修飾DNAの開発を目指し、その鍵化合物となるべき部分的にリン酸トリエステル結合を有するDNAの一般簡便合成法を、先に有機パラジウム化学の基盤に独自に開発した方法を駆使して、確立した(早川)。前年度の引続きRNAのキャップ構造m^7G5'pppGの大量合成法の開発を行い、リン酸の保護に脱離方法の異なる2種類の保護基、すなわちフェニルチオ基と8-キノリル基を用いることによって、これまでの方法に比べてより簡便で大量合成が可能な改良法を案出した(畑)。軸方向に共有結合が可能な光学活性リン(V)ポルフィリンで修飾したオリゴヌクレオチドを創製し、それを用いて、距離依存性の大きい電子移動によるオリゴヌクレオチドのシーケンスの高感度解析法を案出した(清水)。ジヒドロウリジンを含むオリゴヌクレオチド合成に用いるヌクレオシドの調製、[6-^<15>N]アデノシンおよび[4-^<15>N]シチジン誘導体の効果的合成、ならびに2'-0-(α-およびβ-D-リボフラノシル)アデノシンの形式的合成を行った(石戸)。アデノシン-5'-チオホスホロイミダゾリドのウラニルイオン触媒による重合反応を中性水溶液中で行い、保護基をまったく用いる事なく、高位置選択的および高立体選択的にオリゴチオアデニル酸を合成する手法を開発した(沢井)。

研究成果
(21件)

すべてその他

すべて文献書誌 (21件)

[文献書誌] R.Noyori: "Practical Synthesis of 2'-5'-Linked Oligoadenylates(2-5A Oligoners)." Austr.J.Chem.45. 205-225 (1992)
[文献書誌] Y.Hayakawa: "Partial Methyl Phosphotriester-modification of Oligodenxyribo-nucleotides." Nucleic Acids Symp.Ser.27. 103-104 (1992)
[文献書誌] M.Uchiyama: "O-Selective Phosphorylation of Nucleosides without N-Protection." J.Org.Chem. 58. 373-379 (1993)
[文献書誌] R.Iwase: "Molecular Design of a Eukaryotic Messenger RNA and Its Chemical Synthesis." Nucleic Acids Res.20. 1643-1648 (1992)
[文献書誌] Y.Ueno: "Synthesis of 2'(3')-O-(L-Phenylalanyl)and 2'(3')-O-(D-Phenyl-alanyl)Dytidylyl(3'-5)adenosine." Chem.Lett.595-598 (1992)
[文献書誌] S.Ohuchi: "Transformation of Dinucleoside S-Aryl Phosphorothioates into the Corresponding O-Alkyl Phosphates by Use of Tributyltin Alkoxides." Chem.Lett.1501-1504 (1992)
[文献書誌] S.Ohuchi: "Facile Chlorination of Suger Moiety of Nucleosides by Use of Tris(2,4,6-tribromophemoxy)dichlophoshorane." Chem.Lett.1505-1506 (1992)
[文献書誌] S.Ohuchi: "O-Alkylation of Dialkyl Phosphates and O-Alkyl Phosphonates via the Stannyl Intermediates." Nucleosides & Nucleotides. 11. 749-757 (1992)
[文献書誌] S.Makino: "Chemical Synthesis of Cytidine-5'-monophosphono-N-acetyl-neuraminic Acid(CMP-Neu5Ac)." Tertahedron Lett.34. (1993)
[文献書誌] T.Wada: "Nucleoside 3'-N,N-Dialkyphosphonamedates as Noves Nucleotide Units for the Solution-Shase Oligonucleotide Synthesis." Tetrahedron. (1993)
[文献書誌] T.Shimidzu: "Syntheses of Oligonucleotide Derivatives with P(V)-Porphyrin and Their Properties." Nucleic Acids Symp.Ser.27. 97-98 (1992)
[文献書誌] M.Kitamura: "Chiral Phosphoromorphidate Derivatives of Oligothymidylate and Their Hydridization Abilities." Nucleosides & Nucleotides. 11. 473-482 (1992)
[文献書誌] H.Segawa: "Synthesis of Axial Dialkoxy Phosphorus(V)porphyrin Derivatives.Novel Hypervalent Phosphorus Compounds." J.Chem.Soc.,Perkin Trans.1. 939-940 (1992)
[文献書誌] H.Segawa: "Phosphoinduced Axial Bond Exchange Reaction of Dichloro-Phosphorus(V)tetraphenylprophyrin Chloride:Photochemical Activation of Central Three-centre Four-electron Bond through the" J.Chem.Soc.,Chem.Commun.1066-1067 (1992)
[文献書誌] K.Kunimoto: "Selective Synthesis of Unsymmertrical Dialkoxyphosphorus(V)-tetraphenylporphine Derivatives by Stepwise Substitution of Axial Position." Tetrahedron Lett.33. 6327-6330 (1992)
[文献書誌] K.Kamaike: "Further Improvement in the Procedure for Oligonucleotide Synthesis in Terms of a Cellulose Acetate Derivative as a Polymer-support." Nucleosides & Nucleotides. 11. 637-668 (1992)
[文献書誌] H.Sawai: "Synthesis of Cyclic and Acyclic Oligocytidylates by Uranyl Ion Catalyst in Aqueous Solution." J.Chem.Soc.,Perkin Trans.1. 505-508 (1992)
[文献書誌] H.Sawai: "Divalent Metal Ion-Catalyzed Prophoshate Bond Formation in Aqueous Solution.Synthesis of Nucleotides Containing Polyphosphate." Nucleosides & Nucleotides. 11. 773-785 (1992)
[文献書誌] M.Hirai: "Synthesis and DNA Cleaving Activity of Copper Complex of Macrocyclic Compound Containing 1,10-Phenanthroline." Chem.Lett.2023-2026 (1992)
[文献書誌] M.Shimazu: "Facile an Stereoselctive Synthesis of 2'-5' Oligothioadenylates by UO_2^<2+>Ion Catalyst." Nucleic Acids Symp.ser.27. 105-106 (1992)
[文献書誌] K.Shinozuka: "Temperature Dependent Duplex Formation of 3'-Phosphate Bearing α-2'-Deoxyoctathymidylate Phosphorothioate and Polyriboadenylic Acid Complex." Chem.Lett.2209-2212 (1992)

1992 年度 実績報告書

特異な構造をもつRNAの化学合成と反応

研究代表者

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

研究成果

[文献書誌] R.Noyori: "Practical Synthesis of 2'-5'-Linked Oligoadenylates(2-5A Oligoners)." Austr.J.Chem.45. 205-225 (1992)

[文献書誌] Y.Hayakawa: "Partial Methyl Phosphotriester-modification of Oligodenxyribo-nucleotides." Nucleic Acids Symp.Ser.27. 103-104 (1992)

[文献書誌] M.Uchiyama: "O-Selective Phosphorylation of Nucleosides without N-Protection." J.Org.Chem. 58. 373-379 (1993)

[文献書誌] R.Iwase: "Molecular Design of a Eukaryotic Messenger RNA and Its Chemical Synthesis." Nucleic Acids Res.20. 1643-1648 (1992)

[文献書誌] Y.Ueno: "Synthesis of 2'(3')-O-(L-Phenylalanyl)and 2'(3')-O-(D-Phenyl-alanyl)Dytidylyl(3'-5)adenosine." Chem.Lett.595-598 (1992)

[文献書誌] S.Ohuchi: "Transformation of Dinucleoside S-Aryl Phosphorothioates into the Corresponding O-Alkyl Phosphates by Use of Tributyltin Alkoxides." Chem.Lett.1501-1504 (1992)

[文献書誌] S.Ohuchi: "Facile Chlorination of Suger Moiety of Nucleosides by Use of Tris(2,4,6-tribromophemoxy)dichlophoshorane." Chem.Lett.1505-1506 (1992)

[文献書誌] S.Ohuchi: "O-Alkylation of Dialkyl Phosphates and O-Alkyl Phosphonates via the Stannyl Intermediates." Nucleosides & Nucleotides. 11. 749-757 (1992)

[文献書誌] S.Makino: "Chemical Synthesis of Cytidine-5'-monophosphono-N-acetyl-neuraminic Acid(CMP-Neu5Ac)." Tertahedron Lett.34. (1993)

[文献書誌] T.Wada: "Nucleoside 3'-N,N-Dialkyphosphonamedates as Noves Nucleotide Units for the Solution-Shase Oligonucleotide Synthesis." Tetrahedron. (1993)

[文献書誌] T.Shimidzu: "Syntheses of Oligonucleotide Derivatives with P(V)-Porphyrin and Their Properties." Nucleic Acids Symp.Ser.27. 97-98 (1992)

[文献書誌] M.Kitamura: "Chiral Phosphoromorphidate Derivatives of Oligothymidylate and Their Hydridization Abilities." Nucleosides & Nucleotides. 11. 473-482 (1992)

[文献書誌] H.Segawa: "Synthesis of Axial Dialkoxy Phosphorus(V)porphyrin Derivatives.Novel Hypervalent Phosphorus Compounds." J.Chem.Soc.,Perkin Trans.1. 939-940 (1992)

[文献書誌] H.Segawa: "Phosphoinduced Axial Bond Exchange Reaction of Dichloro-Phosphorus(V)tetraphenylprophyrin Chloride:Photochemical Activation of Central Three-centre Four-electron Bond through the" J.Chem.Soc.,Chem.Commun.1066-1067 (1992)

[文献書誌] K.Kunimoto: "Selective Synthesis of Unsymmertrical Dialkoxyphosphorus(V)-tetraphenylporphine Derivatives by Stepwise Substitution of Axial Position." Tetrahedron Lett.33. 6327-6330 (1992)

[文献書誌] K.Kamaike: "Further Improvement in the Procedure for Oligonucleotide Synthesis in Terms of a Cellulose Acetate Derivative as a Polymer-support." Nucleosides & Nucleotides. 11. 637-668 (1992)

[文献書誌] H.Sawai: "Synthesis of Cyclic and Acyclic Oligocytidylates by Uranyl Ion Catalyst in Aqueous Solution." J.Chem.Soc.,Perkin Trans.1. 505-508 (1992)

[文献書誌] H.Sawai: "Divalent Metal Ion-Catalyzed Prophoshate Bond Formation in Aqueous Solution.Synthesis of Nucleotides Containing Polyphosphate." Nucleosides & Nucleotides. 11. 773-785 (1992)

[文献書誌] M.Hirai: "Synthesis and DNA Cleaving Activity of Copper Complex of Macrocyclic Compound Containing 1,10-Phenanthroline." Chem.Lett.2023-2026 (1992)

[文献書誌] M.Shimazu: "Facile an Stereoselctive Synthesis of 2'-5' Oligothioadenylates by UO_2^<2+>Ion Catalyst." Nucleic Acids Symp.ser.27. 105-106 (1992)

[文献書誌] K.Shinozuka: "Temperature Dependent Duplex Formation of 3'-Phosphate Bearing α-2'-Deoxyoctathymidylate Phosphorothioate and Polyriboadenylic Acid Complex." Chem.Lett.2209-2212 (1992)

1992 年度実績報告書

早川芳宏名古屋大学, 大学院人間情報学研究科, 教授 (50022702)