Structural analysis of the binding modes of minor groove ligands comprisedof disubstituted benzenes

Two-dimensional homonuclear NMR was used to characterize synthetic DNA mino r groove-binding ligands in complexes with oligonucleotides containing thre e different A-T binding sites, The three ligands studied have a C-2 axis of symmetry and have the same general structural motif of a central para-subs tituted benzene ring flanked by two meta-substituted rings, giving the mole cules a crescent shape,As with other ligands of this shape, specificity see ms to arise from a tight fit in the narrow minor groove of the preferred A- T-rich sequences, We found that these ligands slide between binding subsite s, behavior attributed to the fact that all of the amide protons in the lig and backbone cannot hydrogen bond to the minor groove simultaneously.