Development of small molecules that stabilize i-motif DNA structures composed in the C-rich regions.

2015 Fiscal Year Final Research Report

• Project/Area Number: 26560444
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• 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)
• 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)
• Project Period (FY): 2014-04-01 – 2016-03-31
• 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.

Free Research Field

ケミカルバイオロジー