title: Selective inhibition of DNA gyrase in vitro by a GC specific eight-ring hairpin polyamide at nanomolar concentration.
abstract: The influence of an eight-ring hairpin DNA minor groove binder on the gyrase mediated DNA supercoiling and cleavage reaction step of the enzyme was investigated. The results demonstrate that supercoiling is affected by the hairpin polyamide in the millimolar concentration range while the enzyme catalyzed cleavage of a 162 bp fragment of pBR322 containing a single strong gyrase site is effectively inhibited at nanomolar concentration. As demonstrated by footprint analysis the latter effect is caused by a specific binding of the hairpin forming polyamide to the enzyme recognition site (GGCC), which indicates that the gyrase activity to produce a double strand break is blocked at this site. The pyrrole-imidazole hairpin polyamide is the most potent inhibitor of the gyrase mediated cleavage reaction compared to other known anti-gyrase active DNA binding agents.
authors.affiliation: Institut für Molekularbiologie, Friedrich-Schiller-Universität Jena, Winzerlaer Str. 10, D-07745, Jena, Germany. simon@hodler.molebio.uni-jena.de
authors.forename: H
authors.initials: H
authors.lastname: Simon
authors.forename: L
authors.initials: L
authors.lastname: Kittler
authors.forename: E
authors.initials: E
authors.lastname: Baird
authors.forename: P
authors.initials: P
authors.lastname: Dervan
authors.forename: C
authors.initials: C
authors.lastname: Zimmer
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018983:DNA Footprinting; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004278:DNA, Superhelical / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009757:Nylons / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D010957:Plasmids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D013302:Streptomyces / Q000201:enzymology; D013379:Substrate Specificity; D059005:Topoisomerase II Inhibitors
chemical_list: D004278:DNA, Superhelical; D009757:Nylons; D059005:Topoisomerase II Inhibitors; D004247:DNA; D003850:Deoxyribonuclease I; D004250:DNA Topoisomerases, Type II