Minimal Thioflavin T Modifications Improve Visual Discrimination of Guanine-Quadruplex Topologies and Alter Compound-Induced Topological Structures

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• 作者：Yuka Kataoka ; Hiroto Fujita ; Yuuya Kasahara ; Toshitada Yoshihara ; Seiji Tobita ; Masayasu Kuwahara
• 刊名：Analytical Chemistry
• 出版年：2014
• 出版时间：December 16, 2014
• 年：2014
• 卷：86
• 期：24
• 页码：12078-12084
• 全文大小：425K
• ISSN：1520-6882

文摘

We newly synthesized thioflavin T (ThT) analogs for which the methyl group at the N3 position on the benzothiazole ring was replaced with either a ((p-(dimethylamino)benzoyl)oxy)ethyl group (ThT-DB) or a hydroxyethyl group (ThT-HE). In several neutral buffers, ThT-HE bound to a parallel guanine-quadruplex (G4) DNA and selectively emitted strong fluorescence at 74- to 240-fold higher intensities than those in the presence of double-stranded DNA (dsDNA), whereas ThT resulted in only 13- to 25-fold higher intensities. Furthermore, circular dichroism (CD) analyses using ThT, ThT-DB, and ThT-HE showed that these compounds could induce topological changes in G4. In addition, the different chemical structures of the N3 substituents could alter a G4鈥揇NA conformation. These results indicate a great potential for N3-substituted ThT analogs as G4 probes and drug leads to achieve gene expression regulation.