Kopaczynska M, Schulz A, Fraczkowska K, Kraszewski S, Podbielska H, Fuhrhop J H
Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland.
Institut für Chemie and Biochemie, Organische Chemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.
Eur Biophys J. 2016 May;45(4):287-99. doi: 10.1007/s00249-015-1095-9. Epub 2015 Dec 8.
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.
研究了氨基糖苷类抗生素对双链DNA结构的凝聚作用。小分子对DNA的选择性凝聚是生物技术中一种有趣的方法。在此，我们展示了小牛胸腺DNA与三种抗生素分子（妥布霉素、卡那霉素和新霉素）之间的相互作用。应用了多种技术来研究这种作用。原子力显微镜、透射电子显微镜图像和核磁共振谱表明，妥布霉素与双链DNA的相互作用导致了棒状、环形和球状结构的形成以及DNA链的强烈凝聚，而在实验中使用的其他氨基糖苷类药物的情况下未观察到这种现象。研究小分子与DNA相互作用的机制对于理解它们在细胞中的功能、设计新的高效药物或尽量减少其不良副作用具有重要意义。使用分子动力学模拟对妥布霉素与DNA双螺旋之间的特异性相互作用进行了建模。模拟研究表明氨基糖苷类对弯曲DNA双螺旋具有特异性，揭示了环形形成的起源。这种现象可能会减轻氨基糖苷类抗生素在人体中的耳毒性或肾毒性问题，以及其他不良反应。
