NDI-induced Topological Conversion of Human Telomeric G-Quadruplexes from Hybrid-2 to Parallel Form

Abstract

G-Quadruplexes(GQs), which are formed by G-rich DNA sequences in human telomeres, have become an attractive target for cancer treatment. The ligands to stabilize the conformation of human telomeric GQs in vivo are particularly important for structure-based ligand design and drug development targeting the noncanonical DNA structure. Here we report the conformational conversion of Tel26 induced by a naphthalene diimide(NDI) ligand in K⁺ buffer, even at cellular physiological temperature(37 °C) and under mimetic cellular crowding conditions created by Ficoll 70. We provide an insight into the dynamic conversion from initial hybrid-2 GQ topology to final parallel GQ topology. These results are helpful for the design of ligands with GQ conformation regulation.

Keywords

G-Quadruplex / Naphthalene diimide / Topological conversion / Telomeric DNA

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