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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00249-015-1095-9) contains supplementary material, which is available to authorized users.
Highlights
Genetic information is accumulated in a double helix of DNA
Defining the bend angle as the angle of normal vectors of the first and last base pairs plains, we found that free DNA double helix with given bases sequence is dynamically bend with the angle 1.9° ± 1.0° per base pair, while binding of the first tobramycin molecule induces the higher bend angle of 2.5° ± 0.8° per base pair with restriction of DNA dynamics seen in standard deviation decrease
We present for the first time a comparative in vitro study of the effects of three natural aminoglycoside antibiotics—tobramycin, kanamycin, and neomycin on the tertiary structure of DNA
Summary
Since genomic DNA is a very long molecule, it must be condensed to fit into a small space of cell nucleus or a virus particle. It must be readily accessible for various activities such as replication and gene expression. Nucleic acids in solution are highly charged biopolymers. This fact considerably complicates tight packing of DNA due to the repulsion between strands. DNA of the human genome is wrapped around positively charged histone octamers and packed into chromosomes (O’Donnell et al 2013; Hirano 2014)
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