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Preparation of Artificial Ribonucleases and Their Applications to the Therapy for Cancer and AIDS

Research Project

Project/Area Number 08559005
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 広領域
Research InstitutionGraduate School of Engineering, The University of Tokyo

Principal Investigator

KOMIYAMA Makoto  Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Professor., 大学院・工学系研究科, 教授 (50133096)

Co-Investigator(Kenkyū-buntansha) SUMAOKA Jun  Department of Chemistry and Biotechnology, Graduate School of Engineering, The U, 大学院・工学系研究科, 助手 (10280934)
YASHIRO Morio  Department of Chemistry and Biotechnology, Graduate School of Engineering, The U, 大学院・工学系研究科, 助教授 (30192785)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1997: ¥3,200,000 (Direct Cost: ¥3,200,000)
KeywordsRNA / Hydrolysis / Oligoamine / Artificial ribonuclease / Cancer / AIDS / Therapy / アミン
Research Abstract

With the aims to develop new therapeutic methods for cancer and AIDS,artificial ribonucleases have been prepared, and RNA scission mechanism is investigated. It is confirmed that intramolecular acid/base cooperation is responsible for the remarkable catalysis of oligoamines for RNA hydrolysis. Novel artificial ribonucleases in which oligoamines are attached inside of DNA oligomers (which are complementary with a part of the substrate RNA) have been synthesized. These artificial enzymes cut the target RNA more precisely than the ones with the scissors at the ends of DNA oligomers, mainly because the scissors are fixed in the rigidly structured double strands. Furthermore, Conjugates of an intercalator and either glycine or iminodiacetate show effective scission of RNA.These conjugates are neutral or negatively charged, which is highly in contrast with the fact that the previously reported RNA scissors are positively charged. Thus, they can be placed exactly at the desired site, even in a strong electrostatic field induced by RNA.These artificial ribonucleases cleave only the target RNA in cells, and thus should be highly potent for the therapy of cancer and AIDS.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Masaki Endo et al.: "Novel phosphoramidite monomer for the site-selective incorporation of a diastereochemically pure phosphoramidate to oligo-nucleotide." J.Org.Chem.61(6). 1994-2000 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masayuki Endo et al.: "RNA hydorolysis by cooperation of carboxlate ion and ammonium ion." J.Am.Chem.Soc.118. 5478-5479 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masayuki Endo et al: "Site-selective RNA hydorolysis by a novel ribo-nuclease:Interposition of oligoamine between two DNA oligomers." Nucleic Acids,Symp.Ser.35. 81-82 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Makato Komiyama et al: "KInetic analysis of deamine-catalyzed RNA hydorolysis." J.Org.Chem.62(7). 2155-2160 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masayuki Endo et al: "Molecular design for a pinpoint RNA scission.Interposition of oligoamines beween two DNA oligomers." J.Org.Chem.62(4). 846-852 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Akinori Kuzuya et al.: "せquence-selective RNA scission by oligoamine-DNA conjigates." Nucleic Asids,Symp.Ser.37. 209-210 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 浅沼 浩之: "人工酸素の構築とその応用" 遺伝. 51(4). 51-56

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 小宮山 真 他: "核酸による超分子形成と人工制限酵素の構築" 季刊化学総説. 31. 196-205

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 小宮山 真 他: "巨大なDNAを正確に切断するスーパー制限酵素の構築" 生物物理. 37(3). 126-129

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 八代 盛夫: "酵素に学ぶ-多核金属錯体の設計と人工ヌクレアーゼへの応用" 化学と工業. 50(7). 980-982

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Endo and M.Komiyama: ""Nove phosphoramidite monomer for the site-selective incorporation of a diastereochemically pure phosphoramidate to oligo-nucleotide."" J.Org.Chem.61(6). 1994-2000 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Endo, K.Hirata, T.Ihara, S.Sueda, M.Takagi, and M.Komiyama: ""RNA hydrolysis by the cooperation of carboxylate ion and ammonium ion."" J.Am.Chem.Soc.118. 5478-5479 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Endo, Y.Azuma, and M.Komiyama: ""Site-selective RNA hydrolysis by a novel artificial ribo-nuclease : Interposition of oligoamine between two DNA oligomers."" Nucleic Acids, Symp.Ser.35. 81-82 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Komiyama and K.Yoshinari: ""Kinetic analysis of diaminecatalyzed RNA hydrolysis."" J.Org.Chem.62(7). 2155-2160 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Endo, Y.Azuma, Y.Saga, A.Kuzuya, G.Kawai, and M.Komiyama: ""Molecular design for a pinpoint RAN scission. Interposition of oligoamines between two DNA oligomers."" J.Org.Chem.62(4). 846-852 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] A.Kuzuya, Y.Azuma, T.Inokawa, K.Yoshinari, and M.Komiyama: ""Sequence-selective RNA scission by oligoamine-DNA conjugates."" Nucleic Acids, Symp.Ser.37. 209-210 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masayuki Endo et al.: "Molecular design for a pinpoint RNA scission. Interposition of oligoamines between two DNA oligomers." J.Org.Chem.62(4). 846-852 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Makoto Komiyama et al.: "Kinetic analysis of diamine-catalyzed RNA hydrolysis." J.Org.Chem.62(7). 2155-2160 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Akinori Kuzuya et al.: "Sequence-selective RNA scission by oligoamine-DNA conjugates." Nucleic Acids,Symp.Ser.37. 209-210 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Endo et al.: "RNA hydrolysis by the cooperation of carboxylate ion and ammonium ion" J.Am.Chem.Soc.118. 5478-5479 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Endo et al.: "Site-selective RNA hydrolysis by a novel artificial ribonuclease:Interposition of oligoamine between two DNA oligomers" Nucleic Acids,Symp.Ser.35. 81-82 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Endo et al.: "Molecular design for a pinpoint RNA scission.Interposition of oligoamine between two DNA oligomers." J.Org.Chem. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Komiyama et al.: "Kinetic study on the diamine-catalyzed RNA hydrolysis" J.Org.Chem.(in press).

    • Related Report
      1996 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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