Footprinting studies of the interaction of quinomycin antibiotic UK63052 with DNA: comparison with echinomycin.

The interaction between UK63052, a novel derivative of the quinomycin group of bifunctional intercalating antibiotics, with DNA has been investigated by footprinting techniques and the results compared with echinomycin. UK63052 binds strongly but reversibly to DNA and decreases the gel mobility of most DNA fragments, although the mobility of bent kinetoplast DNA is increased. The drug binds selectively to the dinucleotide CpG though not all such sequences present good binding sites. Binding is best when CG is surrounded by AT base pairs. UK63052 and echinomycin have different effects on DNA structure as assessed by changes in the sensitivity to modification by diethylpyrocarbonate. The results are interpreted by suggesting that substitutions on the chromophores affect the precise details of DNA recognition.