The natural product prodigiosin binds G-quadruplex DNA

Prodigiosin, a metabolite isolated from Serratia bacteria, is a potent anti-cancer agent. The goal of this research was to determine if prodigiosin could bind to G-quadruplex DNA. We found by using UV–vis spectroscopy that the G-quadruplex K⁺√d[TG₄T]₄, but not the single-stranded Li⁺√d[TG₄T], increased the water solubility of prodigiosin. In addition, we found that prodigiosin's fluorescence was strongly enhanced in the presence of K⁺√d[TG₄T]₄, further evidence for quadruplex-ligand binding. Using ¹H and ³¹P NMR experiments, we confirmed that prodigiosin binds at the 3′-end of K⁺√d[TG₄T]₄. Saturation transfer difference NMR experiments, done by irradiating the G5 H8 signal in K⁺√d[TG₄T]₄, indicated specific interactions between the G-quadruplex and prodigiosin's A and B rings. This study raises the possibility that G-quadruplex DNA may well be a target for the anti-cancer agent prodigiosin.