Interaction of aminoglycosides and their copper(ii) complexes with nucleic acids: implication to the toxicity of these drugs

Abstract

Cupric complexes of eight aminoglycosidic antibiotics were screened for their specific behavior towards tRNA^Phe, both in oxidative and neutral surrounding. Without H₂O₂, the cleavage efficiency was dependent on the resultant charge of the molecule. A comparative assay using tRNA^Phe 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.