The interaction of propidium diiodide with self-complementary dinucleoside monophosphates

Abstract

The interactions of a quinacrine derivative, methylated at both the aromatic and aliphatic nitrogens, and propidium diiodide with the dinucleoside monophosphates CpG, GpC, UpA and ApU have been investigated using 13C-NMR (for the quinacrine derivative prepared with [ 13C]methyl substituents and 1H-NMR and ultraviolet-visible spectroscopy. The quinacrine derivative displayed negligible interaction with the dinucleosides at concentrations up to 5 · 10 −4 M. Propidium did form complexes with dinucleosides even at concentrations as low as 10 −4 M. Propidium displayed a pyrimidine-purine binding preference and gave especially large changes in ultraviolet-visible and 1H-NMR spectra in the presence of CpG. This suggests that propidium forms an intercalated complex with a Watson-Crick hydrogen-bonded CpG dimer. At higher concentrations UpA and GpC gave similar spectral changes indicating that they could also form significant amounts of an intercalated complex with propidium under appropriate conditions. The changes caused by ApU were small under all conditions and were more similar to the effects caused by mononucleotides. These results indicate that, at least for phenanthridines, cationic side chains do not greatly inhibit complex formation with dinucleoside monophosphates, and suggest that the weak interaction of the quinacrine derivative with dinucleosides is due to weaker interactions of the acridine ring system with nucleoside bases relative to the phenanthridine ring system.