title: Selective condensation of DNA by aminoglycoside antibiotics.
abstract: The condensing effect of aminoglycoside antibiotics on the structure of double-stranded DNA was examined. The selective condensation of DNA by small molecules is an interesting approach in biotechnology. Here, we present the interaction between calf thymus DNA and three types of antibiotic molecules: tobramycin, kanamycin, and neomycin. Several techniques were applied to study this effect. Atomic force microscopy, transmission electron microscopy images, and nuclear magnetic resonance spectra showed that the interaction of tobramycin with double-stranded DNA caused the rod, toroid, and sphere formation and very strong condensation of DNA strands, which was not observed in the case of other aminoglycosides used in the experiment. Studies on the mechanisms by which small molecules interact with DNA are important in understanding their functioning in cells, in designing new and efficient drugs, or in minimizing their adverse side effects. Specific interactions between tobramycin and DNA double helix was modeled using molecular dynamics simulations. Simulation study shows the aminoglycoside specificity to bend DNA double helix, shedding light on the origins of toroid formation. This phenomenon may lighten the ototoxicity or nephrotoxicity issues, but also other adverse reactions of aminoglycoside antibiotics in the human body.
authors.affiliation: Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland. marta.kopaczynska@pwr.edu.pl.
authors.forename: M
authors.initials: M
authors.lastname: Kopaczynska
authors.affiliation: Institut für Chemie and Biochemie, Organische Chemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schulz
authors.affiliation: Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Fraczkowska
authors.affiliation: Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland.
authors.forename: S
authors.initials: S
authors.lastname: Kraszewski
authors.affiliation: Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland.
authors.forename: H
authors.initials: H
authors.lastname: Podbielska
authors.affiliation: Institut für Chemie and Biochemie, Organische Chemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.
authors.forename: J H
authors.initials: JH
authors.lastname: Fuhrhop
mesh_terms: D000617:Aminoglycosides / Q000009:adverse effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D002417:Cattle; D004247:DNA / Q000737:chemistry*; D059371:DNA, B-Form / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation / Q000187:drug effects*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D059371:DNA, B-Form; D004247:DNA
keywords: Aminoglycoside antibiotics; Atomic force microscopy; Deoxyribonucleic acid condensation; Electron microscopy; Molecular dynamics; Toroids