title: Sequence-specific binding of luzopeptin to DNA.
abstract: We have examined the binding of luzopeptin, an antitumor antibiotic, to five DNA fragments of varying base composition. The drug forms a tight, possibly covalent, complex with the DNA causing a reduction in mobility on nondenaturing polyacrylamide gels and some smearing of the bands consistent with intramolecular cross-linking of DNA duplexes. DNAase I and micrococcal nuclease footprinting experiments suggest that the drug binds best to regions containing alternating A and T residues, although no consensus di- or trinucleotide sequence emerges. Binding to other sites is not excluded and at moderate ligand concentrations the DNA is almost totally protected from enzyme attack. Ligand-induced enhancement of DNAase I cleavage is observed at both AT and GC-rich regions. The sequence selectivity and characteristics of luzopeptin binding are quite different from those of echinomycin, a bifunctional intercalator of related structure.
authors: Department of Pharmacology, University of Cambridge, UK.
authors: K R
authors: KR
authors: Fox
authors: H
authors: H
authors: Davies
authors: G R
authors: GR
authors: Adams
authors: J
authors: J
authors: Portugal
authors: M J
authors: MJ
authors: Waring
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000494:pharmacology; D004448:Echinomycin / Q000378:metabolism; D006912:Hydroxyquinolines; D007364:Intercalating Agents; D008836:Micrococcal Nuclease / Q000494:pharmacology; D011804:Quinolines / Q000378:metabolism; D047630:Depsipeptides
chemical_list: D000903:Antibiotics, Antineoplastic; D004268:DNA-Binding Proteins; D003850:Deoxyribonuclease I; D004448:Echinomycin; D006912:Hydroxyquinolines; D007364:Intercalating Agents; D008836:Micrococcal Nuclease; D011804:Quinolines; C029831:luzopeptins; D047630:Depsipeptides