title: Studies of viomycin, an anti-tuberculosis antibiotic: copper(ii) coordination, DNA degradation and the impact on delta ribozyme cleavage activity.
abstract: Viomycin is a basic peptide antibiotic, which is among the most effective agents against multidrug-resistant tuberculosis. In this paper we provide the characteristics of its acid base properties, coordination preferences towards the Cu(ii) ions, as well as the reactivity of the resulting complexes against plasmid DNA and HDV ribozyme. Careful coordination studies throughout the wide pH range allow for the characterisation of all the Cu(ii)-viomycin complex species. The assignment of proton chemical shifts was achieved by NMR experiments, while the DTF level of theory was applied to support molecular structures of the studied complexes. The experiments with the plasmid DNA reveal that at the physiological levels of hydrogen peroxide the Cu(ii)-viomycin complex is more aggressive against DNA than uncomplexed metal ions. Moreover, the degradation of DNA by viomycin can be carried out without the presence of transition metal ions. In the studies of antigenomic delta ribozyme catalytic activity, viomycin and its complex are shown to modulate the ribozyme functioning. The molecular modelling approach allows the indication of two different locations of viomycin binding sites to the ribozyme.
authors.affiliation: Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland. kamila.stokowa-soltys@chem.uni.wroc.pl malgorzata.jezowska-bojczuk@chem.uni.wroc.pl.
authors.forename: K
authors.initials: K
authors.lastname: Stokowa-Sołtys
authors.affiliation: Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland. kamila.stokowa-soltys@chem.uni.wroc.pl malgorzata.jezowska-bojczuk@chem.uni.wroc.pl.
authors.forename: N A
authors.initials: NA
authors.lastname: Barbosa
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Kasprowicz
authors.affiliation: Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland. kamila.stokowa-soltys@chem.uni.wroc.pl malgorzata.jezowska-bojczuk@chem.uni.wroc.pl.
authors.forename: R
authors.initials: R
authors.lastname: Wieczorek
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena Via Aldo Moro, 2-53100 Siena, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Gaggelli
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena Via Aldo Moro, 2-53100 Siena, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Gaggelli
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena Via Aldo Moro, 2-53100 Siena, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Valensin
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Wrzesiński
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Ciesiołka
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Kuliński
authors.affiliation: Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland. kamila.stokowa-soltys@chem.uni.wroc.pl malgorzata.jezowska-bojczuk@chem.uni.wroc.pl.
authors.forename: W
authors.initials: W
authors.lastname: Szczepanik
authors.affiliation: Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland. kamila.stokowa-soltys@chem.uni.wroc.pl malgorzata.jezowska-bojczuk@chem.uni.wroc.pl.
authors.forename: M
authors.initials: M
authors.lastname: Jeżowska-Bojczuk
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D053938:DNA Fragmentation / Q000187:drug effects; D004578:Electron Spin Resonance Spectroscopy; D006860:Hydrogen Bonding; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D011199:Potentiometry; D016337:RNA, Catalytic / Q000737:chemistry / Q000378:metabolism*; D014756:Viomycin / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D056831:Coordination Complexes; D016337:RNA, Catalytic; D003300:Copper; D006861:Hydrogen Peroxide; D014756:Viomycin