DNA sequence recognition by a novel series of minor groove-binding ligands.

We have used quantitative DNase I and hydroxyl radical footprinting with three DNA fragments to examine the sequence-specific recognition of DNA by five novel minor groove-binding ligands which contain a structural motif in which a para-disubstituted benzene ring is flanked by two meta-disubstituted benzene rings. The compounds are all AT-selective and bind better to (AT)6 than (AT)4 sites. The ligands bind more tightly to AATT and TAAT than TTAA, TATA and ATAT, and avoid sequences containing central TpA steps. Different side groups cause subtle changes to the sequence recognition properties of these ligands.