Synthesis of novel chemical ligand that selectively bind to the unstabilized base pairs formed in DNA

• Project/Area Number: 20710179
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Living organism molecular science
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: KOJIMA Naoshi National Institute of Advanced Industrial Science and Technology, ゲノムファクトリー研究部門, 主任研究員 (30356985)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 塩基対 / ミスマッチ塩基対 / 損傷塩基 / 検出 / 低分子リガンド / 疎水性相互作用 / 親水性相互作用 / 合成化学 / 分子認識 / 遺伝子 / 核酸

Research Abstract

本研究では、ミスマッチ塩基対や損傷塩基対のようなDNA二本鎖内に生じる不安定化された部位に対して、選択的に結合する低分子リガンドの開発を目指した。その結果、リガンドへの芳香族基の導入、および陽電荷基の導入がいずれも脱塩基部位への結合を向上させることを示し、脱塩基部位に対して高選択的に結合する小分子リガンドの開発を達成した。

Research Products

• [Journal Article] Construction of highly reactive probes for abasic site detection by introduction of an aromatic and a guanidine residue into an aminooxy group (2009)
  • Author(s): Kojima, N., Takebayashi, T., Mikami, A., Ohtsuka, E., Komatsu, Y.
  • Journal Title: J. Am. Chem. Soc. 131 Pages: 13208-13209
  • Peer Reviewed
• [Journal Article] Efficient synthesis of oligonucleotide conjugates on solid-support using an (aminoethoxycarbonyl)- aminohexyl group for 5'-terminal modification (2009)
  • Author(s): Kojima, N., Takebayashi, T., Mikami, A., Ohtsuka, E., Komatsu, Y.
  • Journal Title: Bioorg. Med. Chem. Lett. 19 Pages: 2144-2147
  • Peer Reviewed
• [Journal Article] Construction of highly reactive probes for abasic site detection by introduction of an aromatic and a guanidine residue into an aminooxy group (2009)
  • Author(s): Naoshi Kojima
  • Journal Title: Journal of the American Chemical Society 131 Pages: 13208-13209
  • Peer Reviewed
• [Journal Article] Efficient synthesis of oligonucleotide conjugates on solid-support using an (aminoethoxycarbonyl)aminohexyl group for 5'-terminal modification (2009)
  • Author(s): Naoshi Kojima
  • Journal Title: Bioorganic and Medicinal Chemistry Letters 19 Pages: 2144-2147
  • Peer Reviewed
• [Journal Article] Development of novel chemical probes to detect abasic sites in DNA (2009)
  • Author(s): Naoshi Kojima
  • Journal Title: Nucleic Acids Symposium Series 53 Pages: 45-46
• [Journal Article] Comparison of the chemical properties of a novel amino-linker with various amino modifications (2008)
  • Author(s): Kojima, N., Takebayashi, T., Mikami, A., Sugino, M., Ohtsuka, E., Komatsu, Y.
  • Journal Title: Nucleic Acids Symp. Ser. 52 Pages: 463-464
• [Journal Article] Construction of an aminooxy derivative for RNA and DNA labeling (2008)
  • Author(s): Komatsu, Y., Kojima, N., Takebayashi, T., Mikami, A., Sugino, M., Ohtsuka, E.
  • Journal Title: Nucleic Acids Symp. Ser. 52 Pages: 393-394
• [Journal Article] Comparison of the chemical properties of a novel amino-linker with various aminomodifications (2008)
  • Author(s): Kojima, N.
  • Journal Title: Nucleic Acids Symposium Series 52 Pages: 463-464
• [Journal Article] Construction of an aminooxy derivative for RNA and DNA labeling (2008)
  • Author(s): Kojima, N.
  • Journal Title: Nucleic Acids Symposium Series 52 Pages: 393-394
• [Presentation] DNA脱塩基部位に高効率で反応する試薬の開発 (2009)
  • Author(s): 小島直、小松知志恵、三上暁子、大塚榮子、小松康雄
  • Organizer: 日本環境変異原学会第38回大会
  • Place of Presentation: 静岡県清水市
  • Year and Date: 2009-11-26
• [Presentation] Development of novel chemical probes to detect abasic sites in DNA (2009)
  • Author(s): 小島直、小松知志恵、三上暁子、大塚榮子、小松康雄
  • Organizer: 第6回国際核酸化学シンポジウム
  • Place of Presentation: 岐阜県高山市
  • Year and Date: 2009-09-29
• [Presentation] Development of novel chemical probes to detect abasic sites in DNA (2009)
  • Author(s): 小島直
  • Organizer: 6^<th> International Symposium on Nucleic Acids Chemistry and 36^<th> Symposium on Nucleic Acids Chemistry
  • Place of Presentation: 岐阜県高山市
  • Year and Date: 2009-09-29
• [Presentation] 新規アミノ化試薬の開発と, 固相上でのオリゴヌクレオチド修飾反応への応用 (2008)
  • Author(s): 小島直、小松知志恵、三上暁子、杉野麻衣子、大塚榮子、小松康雄
  • Organizer: 第18回アンチセンスシンポジウム
  • Place of Presentation: 岐阜県岐阜市
  • Year and Date: 2008-11-17
• [Presentation] 新規アミノ化試薬の開発と、固相上でのオリゴヌクレオチド修飾反応への応用 (2008)
  • Author(s): 小島直
  • Organizer: 第18回アンチセンスシンポジウム
  • Place of Presentation: 岐阜大学
  • Year and Date: 2008-11-17
• [Presentation] Comparison of the chemical properties of a novel amino-linker with various amino modifications (2008)
  • Author(s): 小島直、小松知志恵、三上暁子、杉野麻衣子、大塚榮子、小松康雄
  • Organizer: 第35回核酸化学シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2008-09-11
• [Presentation] Construction of an aminoxy derivative for RNA and DNA labeling (2008)
  • Author(s): 小松康雄、小島直、小松知志恵、三上暁子、杉野麻衣子、大塚榮子
  • Organizer: 第35回核酸化学シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2008-09-11
• [Presentation] Comparison of the chemical properties of a novel amino-linker with various aminomodifications (2008)
  • Author(s): 小島直
  • Organizer: 第35回国際核酸化学シンポジウム
  • Place of Presentation: 京都大学
  • Year and Date: 2008-09-11
• [Presentation] Construction of an aminooxy for RNA and DNA kabeling (2008)
  • Author(s): 小松康雄
  • Organizer: 第35回国際核酸化学シンポジウム
  • Place of Presentation: 京都大学
  • Year and Date: 2008-09-11
• [Remarks]
  • URL: http://unit.aist.go.jp/bpri/bpri-bimo/index.html