Interaction of aminoglycosides and their copper(ii) complexes with nucleic acids: implication to the toxicity of these drugs
Cupric complexes of eight aminoglycosidic antibiotics were screened for their specific behavior towards tRNAPhe, both in oxidative and neutral surrounding. Without H2O2, the cleavage efficiency was dependent on the resultant charge of the molecule. A comparative assay using tRNAPhe devoid of the natural hypermodification in the anticodon loop proved that hypermodification is indispensable for site recognition and subsequent cleavage. The intensity of single and double strand scissions in plasmid DNA also proceeded in a charge-dependent manner. Unlike free antibiotics, their cupric complexes in the presence of H2O2, facilitated plasmid linearisation and degradation. The participation of ROS in those processes was confirmed using NDMA as a reporter molecule, whose consumption was influenced by the protonation state of the complex.