title: Minimal thioflavin T modifications improve visual discrimination of guanine-quadruplex topologies and alter compound-induced topological structures.
abstract: 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-DNA conformation. These results indicate a great potential for N3-substituted ThT analogs as G4 probes and drug leads to achieve gene expression regulation.
authors.affiliation: Graduate School of Science and Technology, Gunma University , 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kataoka
authors.forename: Hiroto
authors.initials: H
authors.lastname: Fujita
authors.forename: Yuuya
authors.initials: Y
authors.lastname: Kasahara
authors.forename: Toshitada
authors.initials: T
authors.lastname: Yoshihara
authors.forename: Seiji
authors.initials: S
authors.lastname: Tobita
authors.forename: Masayasu
authors.initials: M
authors.lastname: Kuwahara
mesh_terms: D052160:Benzothiazoles; D004247:DNA / Q000737:chemistry; D054856:G-Quadruplexes; D009690:Nucleic Acid Conformation; D013050:Spectrometry, Fluorescence; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D052160:Benzothiazoles; D013844:Thiazoles; C009462:thioflavin T; D004247:DNA