Chromomycin, mithramycin, and olivomycin binding sites on heterogeneous deoxyribonucleic acid. Footprinting with (methidiumpropyl-EDTA)iron(II).
The DNA binding sites for the antitumor, antiviral, antibiotics chromomycin, mithramycin, and olivomycin on 70 base pairs of heterogeneous DNA have been determined by using the (methidiumpropyl-EDTA)iron(II) [MPE x Fe(II)] DNA cleavage inhibition pattern technique. Two DNA restriction fragments 117 and 168 base pairs in length containing the lactose operon promoter-operator region were prepared with complementary strands labeled with 32P at the 3' end. MPE x Fe(II) was allowed to partially cleave the restriction fragment preequilibrated with either chromomycin, mithramycin, or olivomycin in the presence of Mg2+. The preferred binding sites for chromomycin, mithramycin, and olivomycin in the presence of Mg2+ appear to be a minimum of 3 base pairs in size containing at least 2 contiguous dG x dC base pairs. Many binding sites are similar for the three antibiotics; chromomycin and olivomycin binding sites are nearly identical. The number of sites protected from MPE x Fe(II) cleavage increases as the concentration of drug is raised. For chromomycin/Mg2+, the preferred sites on the 70 base pairs of DNA examined are (in decreasing affinity) 3'-GGG, CGA greater than CCG, GCC greater than CGA, CCT greater than CTG-5'. The sequence 3'-CGA-5' has different affinities, indicating the importance of either flanking sequences or a nearly bound drug.
D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D014128:Chromomycin A3; D002865:Chromomycins; D004247:DNA; D004492:Edetic Acid / Q000031:analogs & derivatives*; D009848:Olivomycins; D008926:Plicamycin; D013329:Structure-Activity Relationship; D013950:Thymus Gland
D002865:Chromomycins; C038200:methidiumpropyl-EDTA-iron(II); D009848:Olivomycins; D004247:DNA; D004492:Edetic Acid; D014128:Chromomycin A3; D008926:Plicamycin