The natural product prodigiosin binds G-quadruplex DNA

Abstract

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.

Keywords:

• G-quartet
• G-quadruplex
• prodigiosin
• prodigiosene

Acknowledgement

We thank Dr Yiu-Fai Lam for his help and advice with NMR experiments.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We thank the Chemical Sciences, Geosciences, and Biosciences Division, Basic Energy Sciences, US Department of Energy (DE-FG02-98ER14888) for financial support.