Synthesis of quinolinium-based probes and studies of their effects for selective G-quadruplex DNA targeting

Abstract

G-quadruplex DNA structures are prevalent in genomes and are considered to play important roles in many important biological processes, which can be linked to many cancers and human diseases. The development of specific probes for G-quadruplex DNAs is thus of great interest in order to gain a deeper understanding of the role of these structures and functions. Herein, we designed and synthesized two new quinolinium conjugates with different styrene-like side groups as G-quadruplex DNA probes. Results revealed that the substitution pattern gave a great influence on the ability for the discrimination of the G-quadruplex from other DNA structures. Probe R-1 with a flexible side group displayed significant and distinctive changes in both the absorption and fluorescence spectra in the presence of G-quadruplex DNAs. Evaluation of R-1 interactions with G-quadruplex DNAs was further performed with fluorescence and absorption titration, circular dichroism, and molecular docking to validate the selectivity, sensitivity and binding mechanism. In addition, the application of R-1 for living cell imaging was also demonstrated.