title: Iron(II) supramolecular helicates condense plasmid DNA and inhibit vital DNA-related enzymatic activities.
abstract: The dinuclear iron(II) supramolecular helicates [Fe2 L3 ]Cl4 (L=C25 H20 N4 ) bind to DNA through noncovalent (i.e., hydrogen-bonding, electrostatic) interactions and exhibit antimicrobial and anticancer effects. In this study, we show that the helicates condense plasmid DNA with a much higher potency than conventional DNA-condensing agents. Notably, molecules of DNA in the presence of the M enantiomer of [Fe2 L3 ]Cl4 do not form intermolecular aggregates typically formed by other condensing agents, such as spermidine or spermine. The helicates inhibit the activity of several DNA-processing enzymes, such as RNA polymerase, DNA topoisomerase I, deoxyribonuclease I, and site-specific restriction endonucleases. However, the results also indicate that the DNA condensation induced by the helicates does not play a crucial role in these inhibition reactions. The mechanisms for the inhibitory effects of [Fe2 L3 ]Cl4 helicates on DNA-related enzymatic activities have been proposed.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i. Kralovopolska 135, 612 65 Brno (Czech Republic).
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Malina
authors.affiliation: School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT (UK).
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hannon
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i. Kralovopolska 135, 612 65 Brno (Czech Republic). brabec@ibp.cz.
authors.forename: Viktor
authors.initials: V
authors.lastname: Brabec
mesh_terms: D004262:DNA Restriction Enzymes / Q000037:antagonists & inhibitors; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004270:DNA, Circular / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D005296:Ferrous Compounds / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D059004:Topoisomerase I Inhibitors / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004270:DNA, Circular; D004791:Enzyme Inhibitors; D005296:Ferrous Compounds; D059004:Topoisomerase I Inhibitors; D012321:DNA-Directed RNA Polymerases; D004262:DNA Restriction Enzymes; D004264:DNA Topoisomerases, Type I
keywords: DNA; condensation; enzymes; helical structures; inhibition