Recognition of UV-clamaged DNA by antinoglycoside antibiotics
| Project/Area Number |
17205016
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemistry related to living body
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| Research Institution | Osaka University |
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Principal Investigator |
IWAI Shigenori Osaka University, Graduate School of Engineering Science, Professor (10168544)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥40,040,000 (Direct Cost: ¥30,800,000、Indirect Cost: ¥9,240,000)
Fiscal Year 2007: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2006: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2005: ¥31,070,000 (Direct Cost: ¥23,900,000、Indirect Cost: ¥7,170,000)
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| Keywords | DNA / Ultraviolet light / DNA damage / drug-DNA interactions / Molecular recoenition / Surface plasmon resonance |
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| Research Abstract |
It was expected that aminoglycoside antibiotics, which bind to the A-site of 168 rRNA, would also bind to DNA containing the (6-4) photoproduct because the structures of these two nucleic acids are similar to each other. We analyzed DNA binding properties of eleven aminoglycoside by measuring the surface plasmon resonance (SPR). Relatively small dissociation constants were obtained for neomycin, paromomycin, and apramycin, but the difference between damaged and undamaged duplexes was not observed. At the beginning of this project, kanarmydn A showed a selectivity for the photoproduct-containing duplex, but detailed analysis revealed that it was due to the dissociation of the 14-base-pair duplex, which was used for the SPR measurements at that time. This drug had a slightly higher affinity for single-stranded DNA than for the double-stranded one. Since the structural difference between DNA and RNA might cause the negative results, we tested neocaranostatin that recognizes and cleaves bulged DNA, which has a structure almost the same as that of the (6-4) photoproduct-containing DNA, but lesion-specific cleavage was not observed. Then, we tested three amines, which were expected to interact with the three hydrogen-bond acceptors arranged linearly in the (6-4) photoproduct, to search for a molecule that directly recognizes the chemical structure of this lesion, but none of them showed binding. We have discovered an intramolecular hydrogen bond within the (6-4) photoproduct in another study, and this hydrogen bond interferes with the ligand binding. We also analyzed the binding of distamycin A to damaged DNA, which had been found before, in detail, and revealed that this compound recognized the chemical structure of the base pair at the lesion site, not the structural properties of the damaged DNA, and that the (6-4) photoproduct accidentally fulfilled the conditions required for the distamycin A binding.
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Characterization of distamycin A binding to damaged DNA2008
Author(s)
Aki, Inase-Hashimoto, Shinya, Yoshikawa, Yusuke, Kawasaki, Takashi, S., Kodama, Shigenori, Iwai
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Journal Title
Bioorganic and Medicinal Chemistry Vol.16
Pages: 164-170
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Preferential formation of(5S,60-thymine glycol for oligonucleotide synthesis and analysis of drug binding to thymine glycol-containing DNA2006
Author(s)
Tatsuhiko, Shimizu, Koichiro, Manabe, Shinya, Yoshikawa, Yusuke, Kawasaki, Shigenori, Iwai
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Journal Title
Nucleic Acids Research Vol.34
Pages: 313-321
Description
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Related Report
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[Presentation] Spectroscopic studies on a novel intramolecular hydrogen bond within the(6-4) photoproduct2007
Author(s)
Junpei, Yamamoto, Yoshiyuki, Tanaka, Kenichi, Hitomi, Elizabeth, D., Getzoff, Shigenori, Iwai
Organizer
The 5th International Symposium on Nucleic Acids Chemistry
Place of Presentation
Tokyo
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Structural analysis of DNA containing(6-4) photoproduct in complex with distamycin A by NMR2006
Author(s)
Hiroaki, Tsuchibayashi, Takako, Ohyama, Akimasa, Matsugami, Takehiro, Nanjo, Shigenori, Iwai, Masato, Katahira
Organizer
Thirty-third Symposium on Nucleic Acids Chemistry
Place of Presentation
Osaka
Description
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Related Report
