Structural analysis of drug—DNA interactions

Abstract

This review summarizes results of solution NMR and X-ray crystallographic structural studies of drug—DNA complexes that have been reported since December, 1989. These include minor-groove-binding drugs, intercalators, and covalent adducts. Comparison of results obtained for the same or similar drugs bound to different DNA sequences, or complexes studied in solution and in the crystal, indicates the importance of sequence and conditions in determining the mode of drug binding. Different structures are sometimes observed in the crystal and in solution, and the mode of drug binding is sometimes different for different sequences. Two important general conclusions can be drawn from these studies. Firstly, large structural changes are often observed in the DNA concomitant with drug binding — these include widening of the minor groove to accommodate drug dimers and the formation of Hoogsteen base pairs. Secondly, many drugs exhibit more than one binding mode, and therefore one should be cautious in drawing conclusions about the biological mode of action of a drug based on results for a single structure.