Guanine rich nucleic acids can adopt a quadruplex structure organized around four hydrogen bonded guanines in a motif known as the G-quartet and are collectively named G-DNAs. Such G-DNA sequences have been found in telomeric regions of chromosome ends and oncogene promoter regions of humans and other organisms, hinting towards interest in cancer therapeutic strategies. In vitro, certain guanine-rich oligonucleotides self-assemble into cation stabilized supramolecular G-DNA structures called G-wires. The sequence composition of G-wires is such that a parallel strand topology is favored and therefore may show preferential binding with known G-quadruplex ligands. This specific binding makes ligand fluorescence an attractive means for studying G-wires in cancerous cellular systems determining uptake, path, and degradation. In this study, the binding of ligands N-methyl mesoporphyrin (NMM), Thiazole Orange (TO), Methylene Blue, (MB) and Thioflavin T (ThT) were analyzed via fluorimetry and PAGE after G-wire self-assembly. When included in the self-assembly reactions, the ligands NMM, MB, and TO show a concentration dependent attenuation of Na+-stabilized G-wire self-assembly. A competitive binding relationship is suggested between higher order structure formation and ligand binding.

G-qudruplex specific ligands attenuate supramolecular G-DNA assembly

253rd National Meeting (2017)

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