Sequence selective binding of bis-daunorubicin WP631 to DNA

We have used footprinting techniques on a wide range of natural and synthetic footprinting substrates to examine the sequence-selective interaction of the bis-daunorubicin antibiotic WP631 with DNA. The ligand produces clear DNase I footprints that are very different from those seen with other anthracycline antibiotics such as daunorubicin and nogalamycin. Footprints are found in a diverse range of sequences, many of which are rich in GT (AC) or GA (TC) residues. As expected, the ligand binds well to the sequences CGTACG and CGATCG, but clear footprints are also found at hexanucleotide sequences such GCATGC and GCTAGC. The various footprints do not contain any particular unique di-, tri- or tetranucleotide sequences, but are frequently contain the sequence (G/C)(A/T)(A/T)(G/C). All sequences with this composition are protected by the ligand, though it can also bind to some sites that differ from this consensus by one base pair.