Abstract
We previously synthesized thioflavin T (ThT) with a hydroxyethyl group introduced at the N3-position (ThT-HE), which binds predominantly to the parallel G-quadruplex (G4) structure found in c-Myc and emits strong fluorescence. In this study, to investigate the effects of introduced substituents on G4 binding and fluorescence emission, a ThT derivative in which the hydroxyl group of ThT-HE was replaced with an amino group (ThT-AE) was synthesized for the first time. Furthermore, three other N3-modified ThT derivatives (ThT-OE2, ThT-SP, and ThT-OE11) having different substituent structures were synthesized by the N-acylation of the terminal amino group of ThT-AE, and their G4-binding and emission properties were investigated. The results showed that, although ThT-AE shows binding selectivity depending on the type of G4, its emission intensity is significantly decreased as compared to that of ThT-HE. However, ThT-OE11, which features an 11-unit oxyethylene chain attached to the terminal amino group of ThT-AE, regained about one-half of the emission intensity of ThT-HE while retaining selectivity for G4s. Accordingly, ThT-OE11 may be used as a key intermediate for synthesizing the conjugates of G4 binders and probes.
Highlights
G-quadruplex structures, known as non-canonical nucleic acid structures, are likely to occur in sequences rich in guanine
Thioflavin T (ThT) has attracted significant attention since Mohanty et al reported that it can bind G4 structures and emit strong fluorescence with low background emission [10]
Since the N3 -position of thioflavin T (ThT) is closest to the C–C single bond, i.e., the axis of rotation between the rings, it is conceivable that the degree of steric hindrance at this position has a large effect on the degree of rotational freedom
Summary
G-quadruplex structures, known as non-canonical nucleic acid structures, are likely to occur in sequences rich in guanine. Typical examples of G4 structures are parallel, antiparallel hybrid-1, and hybrid-2 types (Figure 1) [1,2]. These G4 structures are present mainly in the telomere and promoter regions, and it has been confirmed that the induction of the structure stabilizes chromosomes, controls replication on–off, and protects the telomere region from telomerase. N3-position probes on G4 binding andcandidates fluorescence the biological significance of G4 structures and develop and drug for emission was investigated. Thioflavin T (ThT) has attracted significant attention since Mohanty et al reported that it can bind G4 structures and emit strong fluorescence with low background emission (i.e., the dye does not emit when it is only bound to dsDNA or ssDNA) [10]. 25, x background fluorescence can be obtained using ThT without removing of probe molecules
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
