Cooperative binding of distamycin-A to DNA in the 2:1 mode

The preference of distamycin-a for A-T rich binding sites has been recognized for many years. NMR was first used to show unambiguously that the closely related drug netropsin bound in the minor groove of B-form DNA. Both NMR and crystallographic studies of complexes of distamycin-A, netropsin, Hoechst 33258, and SN-6999 have been carried out. In all of these studies to date, the drugs are bound deep in the minor groove of an A-T segment. Where the drug is bound, the structure of the minor groove closely matches the shape and width of the drug molecule. In several of the DNAs studied crystallographically, the groove is found to be equally narrow without the drug present.