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CHEMICAL SYNTHESIS OF A NEW MATERIAL OF ANTISENSE NUCLEIC ACID"2"PHOSTHORYLATEDRNAS" DIRETED TOWARD IIS BASIC STRUCTRAL STUDIES AND REGULATION OF EXPRESSION OF HIV VIRUS-

Research Project

Project/Area Number 04453031
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 天然物有機化学
Research InstitutionTOKYO INSTITUTE OF TECHNOLOGY

Principal Investigator

SEKINE Mitsuo  TOKYO INSTITUTE OF TECHNOLOGY, FACULTY OF BIOSCIENCE AND BIOTECHNOLOGY, ASSOCIATE PROFESSOR, 生命理工学部, 助教授 (40111679)

Co-Investigator(Kenkyū-buntansha) WADA Takeshi  TOKYO INSTITUTE OF TECHNOLOGY, FACULTY OF BIOSCIENCE AND BIOTECHNOLOGY, RESEARCH, 生命理工学部, 助手 (90240548)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1993: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1992: ¥4,400,000 (Direct Cost: ¥4,400,000)
KeywordsANTISENCE NUCLEIC ACID / 2'-PHOSPHATE / RNA / CHEMICALSYNTHESIS / HIV / SOLID PHASE SYNTHESIS / ENZYME RESISTANCE / AMIDITE / アンチセンス核酸 / 酸素耐性 / 2'-リン酸化RNA / アミダイト試薬 / エイズ / 環状シリルエーテル / 保護基 / 2'、3'-リン酸基転移 / チオリン酸基
Research Abstract

This year, we have tried to study the development of new organic reactions required for the synthesis of 2'-phosphorylated RNAs. As the result, we have achieved the following results : First, we found that bis(2-cyano-1, 1-diamethylethyl)phosphoryl can be used not only as a 2'-hydroxyl protecting groups but also as a precursor of the 2'-phosphate group. This protected phosphoryl group was found to be quite stable upon removal of a 3', 5-cyclic silyl protecting group with HF/Py in dichloromethane and not to migrate from the 3'-2' hydroxyl functions. This finding led us to realize the construction of key intermediates, 2'-phosphorylated 3'-phosphoramide units which were required throughout this study. The builiding units were utilized for the solid phase synthesis of 2'-phosohorylated yridylate derivatives. We could synthesize 2, 4, 6, and 10mers of 2'-phosphorylated uridylated uridylates in good yields. They were found to be resistant to acid and alkaline conditions as well as enzymatic digestion with spleen phosphodiesterase. In particular, the 10 mer proved to have an unique structure as evidenced by NMR.At the present time, we are studying the binding ability of these new nucleic acid derivatives for target DNA or RNA fragments.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] M.Sekine et al.: "Synthesis of a New Class of 2'-Phosphorylated Oligoribonucleotides Capable of Conversion to Oliqoribonucleotides" Journal of Organic Chemistry. 58. 3204-3208 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Sekine et al.: "First Method for the Direct P-S Bond Formation from Phosphodiesters and Thiols" Natural Products Letters. 1. 293-298 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Sekine et al.: "Selective and Rapid O-Acylation of Hydroxyl Groups of Nucleosides by Phase Transfer Catalysis" Natural Products Letters. 1. 251-256 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Sekine et al.: "Sumultaneous Removal of Two 2-Cyano-1,1-dimethylethyl Groups from Bis(2-Cyano-1,1-dimethylethyl)thymidine 3^1-Phosphate Der." Natural Products Letters. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Sekine et al.: "Synthesis and Properties of N-Tritylthio Nucleoside Dervatives" Journal Chemical Society,Perkin Trans.1. 3087-3093 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Sekine et al.: "Synthesis of a New Class of 2'-Phosphorylated Oligoribonucleotides Capable of Conversion to Oligoribonucleotides" Joumal of Organic Chemistry. 58. 3204-3208 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Sekine et al.: ""First Method for the Direct P-S Bond Formation from Phosphodiesters and Thiols"" Natural Products Letters. 1. 293-298 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Sekine et al.: ""Selective and Rapid O-Acylation of Hydroxyl Groups of Nucleosides by Phase Transfer Catalysis"" Natural Products Letters. 1. 251-256 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Sekine et al.: ""Sumultaneous Removal of Two 2-Cyano-1, 1-dimethylethyl Groups from Bis(2-cyano-1, 1-dimethylethjyl) thimidine 3'-Phosphate Derivatives"" Natural Products Letters. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Sekine et al.: ""Synthesis and Properties of N-Tritylthio Nucleoside Derivatives"" Joumal of Chemical Society, Perkin Trans.1. 3087-3093 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Sekine et al.: "Synthesis of Uridylyl(3'-5')uridine Derivatives Containing 5-(Methylaminomethyl)uridine as a Modified Nucleoside" Nucleosides & Nucleotides. 12. 305-321 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Sekine et al.: "A Modified Uridine in the First Position of the Anticodon of a Minor Species of Arginine tRNA" Eur.Journal of Biochemistry. 216. 369-375 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Sekine et al.: "2-(trimethylsilyl)ethyl as a Phosphate Protecting Group in Oligonucleotide Synthesis" Tetrahedron Letters. 34. 8289-8292 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Sekine et al.: "New Method for Removal of Modigied Trityl and Pixyl Groups by the Use of an Acid Species Generated by Reaction of Diethyl" Nucleosides & Nucleotides. (印刷中).

    • Related Report
      1993 Annual Research Report
  • [Publications] R.Iwase et al.: "Molecular Design of a Eukaryotic Messenger RNA and Its Chemical Synthesis" Nucleic Acids Research. 20. 1643-1648 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] G.Kawai et al.: "Conformational Rigidity of Specific Pyrimidine Residues in TRNA Arises from Posttranscriptional Modifications that Enhance Steric Interaction between the Base and 2'OH" Biochemistry. 31. 1040-1046 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Sekine et al.: "Regioselective O-Methylation of Hydroxyl Groups Via 1、3-Benzodithiol-2-yl Ether Intermediates" Natural Product Letters. 1. 25-28 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Sekine et al.: "Synthesis and Properties of N、N-Dibenzoylated Deoxy-cytidine Derivatives" Natural Product Letters. 1. 135-140 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Sekine et al.: "Synthesis of Adenosine、Guanosine and Cytidine Monomer Building Units Bearing the [[2-(Methylthio)phenyl]thio]-methyl (MPTM) Group as the 2'-OH Protecting Group" Nucleosides & Nucleotides. 11. 679-691 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Sekine et al.: "Syntheses and Properties of Dansylated Deoxycytidine 3'、5'-Bisphosphate Derivatives Useful for 3'-Labeling of Oligoribonucleotides" Nucleosides & Nucleotides. 11. 1713-1730 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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