Controlling anticancer drug mediated G-quadruplex formation and stabilization by a molecular container

Abstract

Controlling of ligand mediated G-quadruplex DNA (GQ-DNA) formation and stabilization is an important and challenging aspect due to its active involvement in many biologically important processes such as DNA replication, transcription, etc. Here, we have demonstrated that topotecan (TPT), a potential anticancer drug, can instigate the formation and stabilization of GQ-DNA (H24 → GQ-DNA) in the absence of Na⁺/K⁺ ions via circular dichroism, fluorescence, NMR, UV melting and molecular dynamics (MD) simulation studies. The primary binding mode of TPT to GQ was found to be stacking at the terminal rather than binding to the groove. We have also reverted this conformational transition (GQ-DNA → H24) using a molecular container, cucurbit[7]uril (CB7), by means of the translocation of the drug (TPT) from GQ-DNA to its nanocavity. Importantly, we have carried out the detection of these conformational transitions using the fluorescence color switch of the drug, which is more direct and simple than some of the other methods that involve sophisticated and complex detection techniques.