Abstract
G-quadruplexes (GQs) have become promising anti-cancer therapeutic targets, which are formed by the folding of a guanine-rich repeat DNA/RNA sequence at human telomeres or oncogene promoters. Polymorphism has been observed for the folding topologies of intramolecular GQs. Here we report the topological conversion of human telomeric GQ induced by naphthalene diimide (NDI) ligands in K+ solution. The ligands selectively induce metastable hybrid-type GQs to highly stable parallel-type GQ at physiological temperature (37 °C) in dilute aqueous solutions and under crowding conditions that mimic cellular bioenvironment. According to spectroscopic analyses, the topological conversion is speculated to undergo stepwise unfolding of hybrid-type GQ through intermediate states to parallel-type GQ. The results will prompt further studies on the designs of ligands with GQ conformation regulation functions and nanotechnological systems based on nucleic acids with dynamic regulation of GQ conformation.
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