Development of DNA-interstrand cross-linking compounds and application to DNA scaffold

• Project/Area Number: 21510239
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: KOMATSU Yasuo 独立行政法人産業技術総合研究所, 生物プロセス研究部門, 研究グループ長 (30271670)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 架橋 / DNA / RNA / アミノオキシ / 安定化 / 酵素 / 疎水的相互作用 / 連結

Research Abstract

We have found that a single molecule containing bis(aminooxy) groups is capable of linking two AP sites, which are produced on "complementary" positions of double-stranded oligonucleotides. The aromatic molecule having two aminooxy groups showed much higher conjugation efficiency than the cross-linker with a straight alkyl chain. The interstrand cross-link(ICL) along with the stacking effect of the aromatic residue could stabilize the ICL duplex. We conducted two kinds of enzymatic reactions on the ICL-DNAs and showed that they have the potential to become stable nanosized scaffolds.

Research Products

• [Journal Article] Interstrand cross-link of DNA by covalently linking a pair of abasic sites (2012)
  • Author(s): Ichikawa, K., Kojima, N., Hirano, Y., Takebayashi, T., Kowata, K. and Komatsu, Y
  • Journal Title: Chem. Commun.(Camb) Volume: 48 Issue: 15 Pages: 2143-2145
  • DOI: 10.1039/c2cc16785a
  • Peer Reviewed
• [Journal Article] End-tether Structure of DNA Alters Electron-transfer Pathway of Redox-labeled Oligo-DNA Duplex at Electrode Surface (2012)
  • Author(s): Mie, Y., Kojima, N., Kowata, K. and Komatsu, Y
  • Journal Title: Chemistry Letters Volume: 41 Issue: 1 Pages: 62-64
  • DOI: 10.1246/cl.2012.62
  • NAID: 130004426305
  • Peer Reviewed
• [Journal Article] Structure of the DNA (6-4) photoproduct dTT(6-4)TT in complex with the 64M-2 antibody Fab fragment implies increased antibody-binding affinity by the flanking nucleotides (2012)
  • Author(s): Hideshi Yokoyama
  • Journal Title: Acta Crystallogr.D.Biol.Crystallogr. Volume: 68 Issue: 3 Pages: 232-238
  • DOI: 10.1107/s0907444912000327
  • Peer Reviewed
• [Journal Article] Size-controlled fabrication of gold nanodome arrays and its application to enzyme electrodes (2011)
  • Author(s): Ikegami, M., Mie, Y., Hirano, Y., Suzuki, M. and Komatsu, Y
  • Journal Title: Colloids and Surfaces A : Physicochemical and Engineering Aspects Volume: 384 Issue: 1-3 Pages: 388-392
  • DOI: 10.1016/j.colsurfa.2011.04.024
  • Peer Reviewed
• [Journal Article] Gold sputtered electrode surfaces enhance direct electron transfer reactions of human cytochrome P450s (2010)
  • Author(s): Mie, Y., Ikegami, M. and Komatsu, Y
  • Journal Title: Electchem. Comm Volume: 12 Issue: 5 Pages: 680-683
  • DOI: 10.1016/j.elecom.2010.03.005
  • Peer Reviewed
• [Journal Article] Hydroxylamine, Oxime and Hydroxamic Acid Derivatives of Nucleic Acids (2010)
  • Author(s): Kojima, N. and Komatsu, Y
  • Journal Title: Hydroxylamines, Oximes and Hydroxamic Acids Volume: 2 Pages: 807-851
  • DOI: 10.1002/9780470682531.pat0514
  • Peer Reviewed
• [Journal Article] DNA, RNAの末端および内部に対する化学修飾法の開発 (2010)
  • Author(s): 小松康雄
  • Journal Title: 生化学 Volume: 82 Pages: 1141-1145
  • NAID: 10027880294
  • URL: http://wwwsoc.nii.ac.jp/jbiochem/magazine/82-12-10.pdf
  • Peer Reviewed
• [Journal Article] Gold sputtered electrode surfaces enhance direct electron transfer reactions of human cytochrome P450s. (2010)
  • Author(s): Yasuhiro Mie
  • Journal Title: Elect.Comm. Volume: 12 Pages: 680-683
  • Peer Reviewed
• [Journal Article] Hydroxylamine, Oxime and Hydroxamic Acid Derivatives of Nucleic Acids. (2010)
  • Author(s): Kojima, N., Komatsu, Y.
  • Journal Title: Hydroxylamines, Oximes and Hydroxamic Acids Volume: 2 Pages: 807-851
  • Peer Reviewed
• [Journal Article] DNA,RNAの末端および内部に対する化学修飾法の開発 (2010)
  • Author(s): 小松康雄
  • Journal Title: 生化学 Volume: 82 Pages: 1141-1145
  • NAID: 10027880294
  • Peer Reviewed
• [Journal Article] 遺伝子解析にかかわる試薬の開発 (2010)
  • Author(s): 小松康雄、小島直
  • Journal Title: Synthesiology Volume: 3 Pages: 223-230
  • 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): Kojima, N., Takebayashi, T., Mikami, A., Ohtsuka, E. and Komatsu, Y
  • Journal Title: J. Am. Chem. Soc Volume: 131 Issue: 37 Pages: 13208-13209
  • DOI: 10.1021/ja904767k
  • 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. and Komatsu, Y
  • Journal Title: Bioorg. Med. Chem. Lett Volume: 19 Issue: 8 Pages: 2144-2147
  • DOI: 10.1016/j.bmcl.2009.02.121
  • Peer Reviewed
• [Journal Article] Construction of highly reactive probes for AP site detection by introduction of an aromatic and a guanidine residues into an aminooxy group. (2009)
  • Author(s): Naoshi Kojima
  • Journal Title: J.Am.Chem.Soc. 131 Pages: 13208-13209
  • Peer Reviewed
• [Journal Article] Development of novel chemical probes to detect abasic sites in DNA. (2009)
  • Author(s): Naoshi Kojima
  • Journal Title: Nucleic Acids Symp.Ser.(Oxf) 53 Pages: 45-46
• [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: Bioorg.Med.Chem.Lett. 19 Pages: 2144-2147
  • Peer Reviewed
• [Journal Article] Electrochemically driven drug metabolism by membranes containing human cytochrome P450. (2009)
  • Author(s): Yasuhiro Mie
  • Journal Title: J.Am.Chem.Soc. 131 Pages: 6646-6647
  • Peer Reviewed
• [Presentation] Effect of End-tether Structure of Redox-DNA on its Electron Transfer Pathway at Electrode Surface (2011)
  • Author(s): 三重安弘、小島直、小綿恵子、小松康雄
  • Organizer: 第38回国際核酸化学シンポジウム
  • Place of Presentation: 北海道大学(北海道)
  • Year and Date: 2011-11-10
• [Presentation] Electrochemical monitoring of enzyme reactions promoted on double stranded DNA (2011)
  • Author(s): 平野悠、市川康平、小島直、小松康雄
  • Organizer: 第38回国際核酸化学シンポジウム
  • Place of Presentation: 北海道大学(北海道)
  • Year and Date: 2011-11-10
• [Presentation] 核酸中のアルデヒド基に反応する試薬の開発と応用 (2011)
  • Author(s): 小松康雄
  • Organizer: 核酸・核タンパク機能性研究会学術集会
  • Place of Presentation: 恵庭リサ-チ・ビジネスパ-ク(北海道)
  • Year and Date: 2011-08-08
• [Presentation] 核酸中のアルデヒド基に反応する試薬の開発と応用 (2011)
  • Author(s): 小松康雄
  • Organizer: 核酸・核タンパク機能性研究会学術集会
  • Place of Presentation: 恵庭リサーチ・ビジネスパーク(北海道)
  • Year and Date: 2011-08-08
• [Presentation] 核酸の活用技術の開発 (2011)
  • Author(s): 小松康雄
  • Organizer: 大通りサテライトセミナー
  • Place of Presentation: R & Bパーク札幌大通サテライト(北海道)
  • Year and Date: 2011-04-26
• [Presentation] 核酸の活用技術の開発 (2011)
  • Author(s): 小松康雄
  • Organizer: 大通りサテライトセミナー
  • Place of Presentation: R&Bパーク札幌大通サテライト(北海道)
  • Year and Date: 2011-04-26
• [Presentation] 2本鎖構造の安定化を目的とした架橋化試薬の開発 (2010)
  • Author(s): 小松康雄
  • Organizer: 第20回アンチセンスシンポジウム
  • Place of Presentation: 甲南大学(神戸)
  • Year and Date: 2010-12-03
• [Presentation] CYPの電極駆動法の開発と高感度な薬物代謝アッセイへの応用 (2010)
  • Author(s): 三重安弘
  • Organizer: 日本薬学会北海道支部第135回例会
  • Place of Presentation: 北海道大学(札幌)
  • Year and Date: 2010-11-27
• [Presentation] 核酸の利用技術 (2010)
  • Author(s): 小松康雄
  • Organizer: 産総研本格研究ワークショップ
  • Place of Presentation: 全日空ホテル(北海道)
  • Year and Date: 2010-07-14
• [Presentation] 核酸の利用技術 (2010)
  • Author(s): 小松康雄
  • Organizer: 産総研本格研究ワークショップ
  • Place of Presentation: 全日空ホテル(札幌)
  • Year and Date: 2010-07-14
• [Presentation] 遺伝子解析に活用する試薬の開発 (2010)
  • Author(s): 小松康雄
  • Organizer: 日本化学会第90年会
  • Place of Presentation: 近畿大学(大阪府)
  • Year and Date: 2010-03-27
• [Presentation] 遺伝子解析に用いる試薬の開発 (2010)
  • Author(s): 小松康雄
  • Organizer: バイオチップコンソーシアム
  • Place of Presentation: 新宿(東京都)
  • Year and Date: 2010-02-23
• [Presentation] Development of novel chemical probes to detect abasic sites in DNA (2009)
  • Author(s): 小島直、竹林知志恵、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: 高山(岐阜県)
  • Year and Date: 2009-09-29
• [Presentation] Recent research on chemical reagents used for genetic analyses (2009)
  • Author(s): 小松康雄
  • Organizer: Franco-Japanese Workshop in Life Sciences
  • Place of Presentation: CNRS(パリ)
  • Year and Date: 2009-09-22
• [Presentation] Recent research on chemical reagents used for genetic analyses. (2009)
  • Author(s): 小松康雄
  • Organizer: Franco-Japanese Workshop in Life Sciences
  • Place of Presentation: CNRS(パリ)
  • Year and Date: 2009-09-22