2015 Fiscal Year Final Research Report
Development of small molecules that stabilize i-motif DNA structures composed in the C-rich regions.
Project/Area Number |
26560444
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Chemical biology
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Research Institution | Tokyo University of Agriculture and Technology |
Principal Investigator |
Nagasawa Kazuo 東京農工大学, 工学(系)研究科(研究院), 教授 (10247223)
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Co-Investigator(Renkei-kenkyūsha) |
HIROKAWA Takatsugu 独立行政法人産業技術総合研究所, 創薬分子プロファイリング研究センター, 研究員 (20357867)
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Project Period (FY) |
2014-04-01 – 2016-03-31
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Keywords | アイモチーフ / DNA高次構造 / リガンド / シトシン / インシリコ / グアニン四重鎖 |
Outline of Final Research Achievements |
i-Motif is one of a non-B DNA structure, which is believed to construct in the C-rich regions in DNA. Since the no i-motif stabilizing compounds have been reported, no information about the function of i-motif has been obtained. In this research we aimed to develop i-mtoif selective interacting molecules, i.e., i-motif ligands. Among our synthetic libraries together with the compounds suggested by the in silico docking studies, we started ca. forty compounds as candidates for i-motif ligands. With the evaluations by FRET melting analysis, CD spectra analysis, and EMAS experiments, we found the compound which selectively stabilize i-motifs derived from telomere, c-kit, c-myc and bcl-2, respectively. Stabilizing ability of the ligand is high, and delta Tm valu was obtained at 20 °C.
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Free Research Field |
ケミカルバイオロジー
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