NMR studies of the complex between the decadeoxynucleotide d-(GCATTAATGC)2 and a minor-groove-binding drug.

Nearly all 1H NMR lines of the complex formed between the bis(quaternary ammonium) heterocycle 4-[p-[p-(4-quinolylamino)benzamido]anilino]pyridine (1, also known as SN 6999) and the decadeoxyribonucleoside nonaphosphate d-(GCATTAATGC)2 were sequentially assigned by using one- and two-dimensional NMR techniques. Intermolecular nuclear Overhauser effects between the ligand and the DNA show that the drug binds in the minor groove of the DNA, interacting with the central A-T base pairs. Over the temperature range from 277 to 313 K, the lifetime of the drug in the DNA binding sites is short relative to the NMR time scale, since fast exchange is observed for all but a few protons. A model for the binding of 1 to d-(GCATTAATGC)2 is proposed, where the drug binds to two equivalent sites covering approximately five A-T base pairs, which assumes exchange of 1 between these two binding sites.