A propeller-like small molecule as a novel G-quadruplex DNA binder: The study of fluorescent sensing property and preferential interactions with human telo21 structure

A new propeller-like small molecule was synthesized with three terminal amino side groups. The molecule was found to be a selective nucleic acid binder towards telo21 G-quadruplex DNA compared with other representative nucleic acids including single-stranded DNA (dA21), duplex DNA (ds26) and RNA. The fluorescent signal of the molecule upon interaction with telo21 G-quadruplex structure shows remarkable enhancement (F_max/F₀ = 17.9) while interaction with other nucleic acids shows the signal enhancement which is less than 2.1. In addition, a good linear relationship of binding signal correlated with the concentration of telo21 DNA was obtained. Molecular docking study was also performed to acquire the binding behaviour and its interaction modes of the molecule with the structure of human telomeric DNA G-quadruplex. The modelling results show that the three conjugated terminal units (dimethylaminobenzyl groups) associated through the ethylene bridges with the central methylated pyridine ring formed a co-planar conformation upon stacking onto the G-quartets via pi-pi stacking interactions. This could be the key reason that the molecule shows excellent fluorescent signal of binding towards telo21 G-quadruplex DNA rather than other types of nucleic acids.