1993 Fiscal Year Annual Research Report

特異な構造をもつRNAの化学合成と反応

Research Project

Project/Area Number	04226105
Research Institution	Nagoya University
Principal Investigator	早川芳宏名古屋大学, 人間情報学研究科, 教授 (50022702)
Co-Investigator(Kenkyū-buntansha)	沢井宏明群馬大学, 工学部, 教授 (70012648) 清水剛夫京都大学, 工学部, 教授 (10025893) 石戸良治東京薬科大学, 薬学部, 教授 (60016037) 畑辻明東京工業大学, 総合理工学研究科, 教授 (00016049)
Keywords	CMP-シアル酸 / キャップ構造 / 2'-O-D-リボフラノシルアデノシン / オリゴヌクレオチドP(V)ポリフィリン誘導体 / 人工光制限酵素 / 5'-ポリリン酸ヌクレオチド
Research Abstract	細胞表面の糖脂質や糖タンパク質の糖鎖末端を、細胞認識に深く関わるシアル酸で酵素的に修飾するための鍵物質であるシチジン-5'-リン酸-シアル酸(CMP-シアル酸)の化学合成に世界で初めて成功するとともに種々のCMP-シアル酸人工誘導体の合成が可能な一般合成法を開発した(早川、畑)。二官能性ホスホリル化剤、O-[8-(5-クロロキノリル)]S-フェニルホスホロチオエートを開発し、これを用いて、真核生物メッセンジャーRNAのキャップ構造部位のオリゴヌクレオチド、m^7G^5pppGおよびm^7G^5pppAを、ヌクレオシドに全く保護基を用いずに大量合成する方法を開発した(畑)。Yeast initiator tRNA^<Met>の構成成分として見い出されている2'-O-(α-およびβ-D-リボフラノシル)アデノシン、ならびにNMRによる核酸構造研究に有用な(2'R)-ならびに(2'S)-[2'-H^2]-2'-デオキシリボヌクレオシドおよび塩基部環外アミノ基^<15>N標識ヌクレオシドの効率的合成法を確立した(石戸)。オリゴヌクレオチド末端をリン(V)ポルフィリンで修飾した新規な光活性オリゴヌクレオチド誘導体を合成し、ピレン-オリゴヌクレオチド誘導体間の直接電子移動を介したオリゴヌクレオチドのシーケンス検出法を創案、実行した。またリン(V)ポルフィリンをオリゴヌクレオチドの主鎖に嵌めた新規な光活性オリゴヌクレオチドを合成し、ポルフィリン部が光誘起直接電子移動によるDNAの切断を行なうことを明かにし、人工制限酵素合成の可能性を示した(清水)。中性条件下、ホリホトリイミダゾリドあるいはホスホトリベンズイミダゾリドをリン酸供与体に、Mg(II)あるいはMn(II)イオンを触媒に用い、ATP、ADP、あるいは2-5Aなどのモノおよびオリゴヌクレオチドの5'-ポリリン酸化物を、対応する5'-モノヌクレオチド類から効率良く調製する方法を開発した(沢井)。

Research Products

(20 results)

All Other

All Publications (20 results)

[Publications] M.Uchiyama: "O-Selective Phosphorylation of Nucleosides without N-protection" J.Org.Chem.58. 373-379 (1993)
[Publications] S.Makino: "Chemical Synthesis of Cytidine-5'-monophosphono-N-acetylneuraminic Acid(CMP-Neu5Ac)" Tetrahedron Lett.34. 2775-2778 (1993)
[Publications] Y.Hayakawa: "O-Allyl Protection of Guanosine and Thymidine Residues in Oligodeoxyribonucleotide Synthesis" J.Org.Chem.58. 5551-5555 (1993)
[Publications] M.Hirose: "Synthesis of Phenylphosphonodiester-Modified Oligodeoxyribonucleotides via the Allyl Protection" Nucleic Acids Symp.Ser.29. 7-8 (1993)
[Publications] Y.Hayakawa: "Allyl Protection in the Synthesis of Oligodeoxyribonucleotide Phosphorothioates" Nucleosides Nucleotides. 13 発表予定. (1994)
[Publications] M.Sekine: "P-S Bond Formation Between Deoxyribonucleoside Phosphodiesters and Thiols by Means of BTCP" Natural Product Lett.1. 293-298 (1993)
[Publications] T.Wada: "Nucleoside 3'-N,N-Dialkylphosphonamidates as Novel Nucleotide Units for Solution-Phase Oligonucleotide Synthesis" Tetrahedron. 49. 2043-2054 (1993)
[Publications] Y.Ueno: "Studies on the Synthesis of Nucleotidyl-peptide Having 5'-Nucleotidyl-(P-O)-serine Phosphodiester Bond" Nucleic Acids Res.21. 4451-4457 (1993)
[Publications] K.Fukuoka: "Convenient and Large Scale Synthesis of the Cap Structure,m^7G^<5'>pppG" Nucleic Acids Symp.Ser.29. 35-36 (1993)
[Publications] K.Fukuoka: "One-Pot Reaction for the Synthesis of m^7G^<5'>pppG and m^7G^<5'>pppA by Using an Activatable Bifunctional Phosphorylating Reagent" Tetrahedron Lett.36 発表予定. (1994)
[Publications] K.Fukuoka: "Large Scale Synthesis of the Cap part in Messenger RNA Using a New Type of Bifunctional Phosphorylating reagent" Nucleosides Nucleotides. 13 発表予定. (1994)
[Publications] H.Segawa: "One-Dimensional Donor Acceptor Phosphorus Porphyrins Linked with Molecular Wire" Synth.Metal. 55-57. 966-971 (199)
[Publications] T.Saito: "Photochemical Cleavage of DNA by Phosphorus(V)porphyrin Derivatives" Nucleic Acids Symp.Ser.29. 127-128 (1993)
[Publications] T.Saito: "Photochemical Cleavage of DNA with Phosphorus(V)porphyrin derivatives" Nucleosides Nucleotides. 13 発表予定. (1994)
[Publications] H.Sawai: "Mg(II)Ion-Mediated Conversion of Mono- and Oligonucleotides to 5'-Polyphosphates in Aqueous Solution" Tetrahedron Lett.34. 4801-4804 (1993)
[Publications] M.Shimazu: "UO_2^<2+> Catalyzed Oligothioadenylate Synthesis with High Regio- and Stereoselectivity" Angew.Chem.Int.Ed.32. 870-872 (1993)
[Publications] K.Shinozuka: "Bifunctional Labeling of DNA with Tris(2-aminoethyl)amine-derived Novel Fluorescent Agent" Bioorg.Med.Chem.Lett.13. 2883-2886 (1993)
[Publications] J.Seki: "Double and Triple Helix Formation of 2'-5' and 3'-5' Oligonucleotides" Nucleic Acids Symp.Ser.29. 71-72 (1993)
[Publications] K.Shinozuka: "Non-radioisotope Labeling of DNA with Multifunctional Labeling Agent" Nucleic Acids Symp.Ser.29. 73-74 (1993)
[Publications] M.Hirai: "Synthesis of New Copper-Complex of Macrocyclic Compound Consisting of 1,10-Phenanthroline,and Its DNA Binding and Cleaving Activity" Bull.Chem.Soc.Jpn.67 発表予定. (1994)

1993 Fiscal Year Annual Research Report

特異な構造をもつRNAの化学合成と反応

Principal Investigator

早川 芳宏 名古屋大学, 人間情報学研究科, 教授 (50022702)

Research Products

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

[Publications] S.Makino: "Chemical Synthesis of Cytidine-5'-monophosphono-N-acetylneuraminic Acid(CMP-Neu5Ac)" Tetrahedron Lett.34. 2775-2778 (1993)

[Publications] Y.Hayakawa: "O-Allyl Protection of Guanosine and Thymidine Residues in Oligodeoxyribonucleotide Synthesis" J.Org.Chem.58. 5551-5555 (1993)

[Publications] M.Hirose: "Synthesis of Phenylphosphonodiester-Modified Oligodeoxyribonucleotides via the Allyl Protection" Nucleic Acids Symp.Ser.29. 7-8 (1993)

[Publications] Y.Hayakawa: "Allyl Protection in the Synthesis of Oligodeoxyribonucleotide Phosphorothioates" Nucleosides Nucleotides. 13 発表予定. (1994)

[Publications] M.Sekine: "P-S Bond Formation Between Deoxyribonucleoside Phosphodiesters and Thiols by Means of BTCP" Natural Product Lett.1. 293-298 (1993)

[Publications] T.Wada: "Nucleoside 3'-N,N-Dialkylphosphonamidates as Novel Nucleotide Units for Solution-Phase Oligonucleotide Synthesis" Tetrahedron. 49. 2043-2054 (1993)

[Publications] Y.Ueno: "Studies on the Synthesis of Nucleotidyl-peptide Having 5'-Nucleotidyl-(P-O)-serine Phosphodiester Bond" Nucleic Acids Res.21. 4451-4457 (1993)

[Publications] K.Fukuoka: "Convenient and Large Scale Synthesis of the Cap Structure,m^7G^<5'>pppG" Nucleic Acids Symp.Ser.29. 35-36 (1993)

[Publications] K.Fukuoka: "One-Pot Reaction for the Synthesis of m^7G^<5'>pppG and m^7G^<5'>pppA by Using an Activatable Bifunctional Phosphorylating Reagent" Tetrahedron Lett.36 発表予定. (1994)

[Publications] K.Fukuoka: "Large Scale Synthesis of the Cap part in Messenger RNA Using a New Type of Bifunctional Phosphorylating reagent" Nucleosides Nucleotides. 13 発表予定. (1994)

[Publications] H.Segawa: "One-Dimensional Donor Acceptor Phosphorus Porphyrins Linked with Molecular Wire" Synth.Metal. 55-57. 966-971 (199)

[Publications] T.Saito: "Photochemical Cleavage of DNA by Phosphorus(V)porphyrin Derivatives" Nucleic Acids Symp.Ser.29. 127-128 (1993)

[Publications] T.Saito: "Photochemical Cleavage of DNA with Phosphorus(V)porphyrin derivatives" Nucleosides Nucleotides. 13 発表予定. (1994)

[Publications] H.Sawai: "Mg(II)Ion-Mediated Conversion of Mono- and Oligonucleotides to 5'-Polyphosphates in Aqueous Solution" Tetrahedron Lett.34. 4801-4804 (1993)

[Publications] M.Shimazu: "UO_2^<2+> Catalyzed Oligothioadenylate Synthesis with High Regio- and Stereoselectivity" Angew.Chem.Int.Ed.32. 870-872 (1993)

[Publications] K.Shinozuka: "Bifunctional Labeling of DNA with Tris(2-aminoethyl)amine-derived Novel Fluorescent Agent" Bioorg.Med.Chem.Lett.13. 2883-2886 (1993)

[Publications] J.Seki: "Double and Triple Helix Formation of 2'-5' and 3'-5' Oligonucleotides" Nucleic Acids Symp.Ser.29. 71-72 (1993)

[Publications] K.Shinozuka: "Non-radioisotope Labeling of DNA with Multifunctional Labeling Agent" Nucleic Acids Symp.Ser.29. 73-74 (1993)

[Publications] M.Hirai: "Synthesis of New Copper-Complex of Macrocyclic Compound Consisting of 1,10-Phenanthroline,and Its DNA Binding and Cleaving Activity" Bull.Chem.Soc.Jpn.67 発表予定. (1994)

早川芳宏名古屋大学, 人間情報学研究科, 教授 (50022702)