1. Structural features and oxidative stress towards plasmid DNA of apramycin copper complex.
- Author
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Balenci D, Bonechi G, D'Amelio N, Gaggelli E, Gaggelli N, Molteni E, Valensin G, Szczepanik W, Dziuba M, Swiecicki G, and Jezowska-Bojczuk M
- Subjects
- Antioxidants pharmacology, Ascorbic Acid pharmacology, Circular Dichroism, Copper metabolism, DNA metabolism, Electron Spin Resonance Spectroscopy, Hydrogen Peroxide pharmacology, Hydrogen-Ion Concentration, Magnetic Resonance Spectroscopy, Models, Chemical, Nebramycin chemistry, Nebramycin metabolism, Oxidants pharmacology, Thermodynamics, Copper chemistry, DNA chemistry, Nebramycin analogs & derivatives, Oxidative Stress drug effects, Plasmids chemistry
- Abstract
The interaction of apramycin with copper at different pH values was investigated by potentiometric titrations and EPR, UV-vis and CD spectroscopic techniques. The Cu(II)-apramycin complex prevailing at pH 6.5 was further characterized by NMR spectroscopy. Metal-proton distances derived from paramagnetic relaxation enhancements were used as restraints in a conformational search procedure in order to define the structure of the complex. Longitudinal relaxation rates were measured with the IR-COSY pulse sequence, thus solving the problems due to signal overlap. At pH 6.5 apramycin binds copper(II) with a 2 : 1 stoichiometry, through the vicinal hydroxyl and deprotonated amino groups of ring III. Plasmid DNA electrophoresis showed that the Cu(II)-apramycin complex is more active than free Cu(II) in generating strand breakages. Interestingly, this complex in the presence of ascorbic acid damages DNA with a higher yield than in the presence of H(2)O(2).
- Published
- 2009
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