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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00249-015-1095-9) contains supplementary material, which is available to authorized users.

Profound Nanoscale Structural and Biomechanical Changes in DNA Helix upon Treatment with Anthracycline Drugs

“…Long-range electrostatic forces were taken into account using the particle mesh Ewald approach [34], and the integration time step was equal to 2 fs. The used CHARMM 36 force field for nucleic acids was completed with parameters for daunorubicin, doxorubicin and epirubicin, based on ab initio quantum mechanics calculations at the B3LYP/6-31+g level of theory, using the Gaussian 2016 suite of programs [35], with a procedure described elsewhere [17].…”

“…By analyzing structural changes, especially in the length or orientation of nucleic acid strands before and after the drug interaction, it can be distinguished whether it interacts with DNA as a result of intercalation, alkylation, binding within the major or minor double helix groove, or a combination of these mechanisms [15,16]. As we have shown previously, also a damaging effect on the nucleic acid strand can be visualized and detected by AFM [17].…”

The Supramolecular Self‐Assembly of Aminoglycoside Antibiotics and their Applications

“…Kopaczynska et al . studied the interaction of aminoglycoside antibiotics tobramycin, kanamycin and neomycin with calf thymus DNA.…”

“…(b) Zoom in hydrogen bond between tobramycin molecule and oxygen of deoxyribose 5‐phosphate and the amine groups of tobramycin. Reprinted from with permission of Wily‐VCH.…”

Comprehensive review of chemical strategies for the preparation of new aminoglycosides and their biological activities

“…Mass spectrometry has also been used to determine AG binding specificity for rRNA. 287 Additionally, NMR was utilized (i) to explore RNA dynamics and structural plasticity in the presence of AGs, 288 (ii) to investigate the selective condensation of DNA by AGs, 289 and (iii) to study AG drug susceptibility in E. coli . 290 More thorough/detailed coverage of interactions of AGs with various targets can be found in other reviews.…”