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

We have used quantitative DNase I and hydroxyl radical footprinting with th ree DNA fragments to examine the sequence-specific recognition of DNA by fi ve novel minor groove-binding ligands which contain a structural motif in w hich 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. Diff erent side groups cause subtle changes to the sequence recognition properti es of these ligands.