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Design and Synthesis of New Recognition Molecules for the Sequence-Selective Triple Helical DNA Formation

Research Project

Project/Area Number 07672269
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

SASAKI Shigeki  KYUSHU UNIVERSITY FACULTY OF PHARMACEUTICAL SCIENCES ASSOCIATE PROFESSOR, 薬学部, 助教授 (10170672)

Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordstriple helix / triplex / DNA / non-natural base / nucleic acid / hydrogen bonding / 3重鎖DNA / トリプルヘリックス / 遺伝発現制御
Research Abstract

The triplex formation between the duplex and a single strand DNA has been shown to inhibit transcription at the specific DNA site, and expected as a new biological tool and a new therapeutic method in the so-called antigene strategy. However, native oligonucleotides can form triplexes only within the major groove of the homopurine-homopyrimidine stretch of DNA,and the triplex is destabilized either at a TA or a CG interrupting site. Thus, for expansion of the target DNA sequence, several groups have been attempting to develop non-native nucleobases for binding a TA or a CG base pair, but these problems have not yet been generally solved. We have designed new nucleobase 1 (BIG or B) to form a base triplet with a CG base pair selectively through Hoogsteen-type hydrogen bonds. In this study, we synthesized the oligonucleotide incorporating the non-native base 1 (B), with which we have investigated triplex formation with several duplex DNAs. As a result, it has been demonstrated that the oligonucleotide incorporating 1 forms triplexes by recognizing a CG base pair within a homopurine-homopyrimidine motif. In addition, it has been also revealed that the new non-native base (2) can stabilize a triplex at a CG site more selectively than 1, and that the selective triplex formation at a TA site is enabled by the new non-native base (3). To our knowledge, these new bases are the first ones that form nonnative-type triplexes selectively with comparable stability with native-type triplexes. Therefore, these non-native bases (1,2,3) will become potential candidates to expand the target sequence containing CG and TA interrupting sites.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Nagatsugi,Fumi: "2-Aminopurine Derivatives with C6-Substituted Olefin as Novel Cross-Linking Agents and the Synthesis of the Corresponding b-Phosphoramidite Precursors" Tetrahedron. (印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mizushima,Tohru: "Molecular Design of Inhibitors of in Vitro oriC DNA Replication Based on the Potential to Block the ATP Binding of DnaA Protein" J.Biol.Chem.,. 271(41). 25178-25183 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagatsugi,Fumi: "Design of Cross-Linking Agent for Activation by Metabolic Oxidation" Nucleic Acids,Symp.Ser.35. 79-80 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakashima,Shouji: "The New Artificial Nucleobases for the Selective Formation of the Non-Natural Type Triple Complex with T-A and C-G Base Pairs" Nucleic Acids,Symp.Ser.35. 105-106 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sasaki,Shigeki: "A New Application of a Peptide Library to Identify Selective Interaction Between Small Peptides in an Attempt to Develop Recognition Molecules toward Protein Surface" Tetrahedron Lett.37(1). 85-88 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sasaki,Shigeki: "Design of a Novel Artificial Nucleobase for the Selective Formation of Triple-Complex with Cytosine-Guanine Base Pair" Tetrahedron Lett.36(52). 9521-9524 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagatsugi, Fumi ; Uemura, Kengo ; Nakashima, Shouji ; Maeda, Minoru ; Sasaki, Shigeki: "6-Vinylated Guanosine as a Novel Cross-Linking Agent and its Versatile Synthesis from the 6-O-Tosylate by Pd (0) -Catalyzed Cross-Coupling" Tetrahedron Letters. 36. 421-424 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sasaki, Shigeki ; Nakashima, Shouji ; Nagatsugi, Fumi ; Tanaka, Yoshitsugu ; Hisatome, Masao ; Maeda Minoru: "Design of a Novel Artificial Nucleobase for the Selective Formation of Triple-Complex with Cytosine-Guanine Base Pair" Tetrahedron Lett.36. 5571-5574 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagatsugi, Fumi, Uemura, Kengo ; Nakashima, Sshouji ; Maeda, Minoru ; Sasaki, Shigeki: "Design and Synthesis of New Cross-Linking Agents" Nucleic Acids, Symp.Series. 34. 171-172 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sasaki, Shigeki ; Takagi, Manabu ; Tanaka, Yoshizugu ; Maeda, Minoru: "A New Application of a Peptide Library to Identify Selective Interaction Between Small Peptides in an Attempt to Develop Recognition Molecules toward Protein Surface" Tetrahedron Lett.37. 85-88 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakashima, Shouji ; Matsuura, Naoko ; Nagatsugi, Fumi ; Maeda, Minoru ; Sasaki, Sasaki: "The New Artificial Nucleobases for the Selective Formation of the Non-Natural Type Triple Complex with T-A and C-G Base Pairs" Nucleic Acids, Symp.Ser.35. 105-106 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagatsugi, Fumi ; Kawasaki, Takesi ; Maeda, Minoru ; Sasaki, Shigeki: "Design of Cross- Linking Agent for Activation by Metabolic Oxidation" Nucleic Acids, Symp.Ser.35. 79-80 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mizushima, Tohru ; Sasaki, Sigeki ; Ohishi, Hiroko ; Kobayashi, Masakatsu ; Katayama, Tsutomu ; Miki, Tateo ; Maeda, Minoru ; Sekimizu, Kazuhisa: "Molecular Design of Inhibitors of in Vitro oriC DNA Replication Based on the Potential to Block the ATP Binding of DnaA Protein" J.Biol.Chem.271(41). 25178-25183 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagatsugi, Fumi ; Uemura, Kengo ; Nakashima, Shouji ; Maeda, Minoru ; Sasaki, Shigeki: "2-Aminopurine Derivatives with C6-Substituted Olefin as Novel Cross-Linking Agents and Synthesis of the Corresponding beta-Phosphoramidite Precursors" Tetrahedron. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagatsugi,Fumi: "2-Aminopurine Derivaties with C6-Substituted Olefin as Novel Cross-Linking Agents and the Synthesis of the Corresponding b-Phosphoramidite Precursors" Tetrahedron. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Mizushima,Tohru: "Molecular Design of Inhibvitors of in Vito oriC DNA Replication Based on the Potential to Block the ATP Binding of DnaA Protein" J.Biol.Chem.,. 271(4). 25178-25183, (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nagatsugi,Fumi: "Design of Cross-Linking Agent for Activation by Metabolic Oxidation" Nucleic Acids,Symp.Ser.35. 79-80 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakashima,Shouji: "The New Artificial Nucleobases for the Selective Formation of the Non-Natural Type Triple Complex with T-A and C-G Base Pairs" Nucleic Acids,Symp.Ser.35. 105-106 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sasaki,Shigeki: "A New Application of a Peptide Library to Identify Selective Interaction Between Small Peptides in an Attempt to Develop Recognition Molecules toward Protein Surface" Tetrahedron Lett.37(1). 85-88 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sasaki,Shigeki: "Design of a Novel Artificial Nucleobase for the Selective Formation of Triple-Complex with Cytosine-Guanine Base Pair" Tetrahedron Lett.36(52). 9521-9524 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiroyuki Naito: "The First Total Synthesis of Natural (+) -Bullatacin and 15,14-bisepi (+) -Bullatacin" J.Org.Chem.60. 4419-4427 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shigeki Sasaki: "New Calcium-Selective Electrodes Based on Annonaceous Acetogenins and Their Analogs with Neighboring Bistetrahydrofuran," Tetrahedron Lett.36. 5571-5574 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shigeki Sasaki: "Design of a Novel Artificial Nucleobase for the Selective Formation of Triple Complex with Cytosine-Guanine Base Pair" Tetrahedron Lett.36. 9521-9524 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fumi Nagatsugi: "Design and Synthesis of New Cross-Linking Agents" Nucleic Acids, Symp. Series. 34. 171-172 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shigeki Sasaki: "A New Application of a Peptide Library to Identify Selective Interaction Between Small Peptides in an Attempt to Develop Recognition Molecules toward Protein Surface." Tetrahedron Lett.36. 85-88 (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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