Studies of viomycin, an anti-tuberculosis antibiotic: Copper(II) coordination, DNA degradation and the impact on delta ribozyme cleavage activity

Viomycin is a basic peptide antibiotic, which is among the most effective agents against multidrug-resistant tuberculosis. In this paper we provide the characteristics of its acid base properties, coordination preferences towards the Cu(II) ions, as well as the reactivity of the resulting complexes against plasmid DNA and HDV ribozyme. Careful coordination studies throughout the wide pH range allow for the characterisation of all the Cu(II)-viomycin complex species. The assignment of proton chemical shifts was achieved by NMR experiments, while the DTF level of theory was applied to support molecular structures of the studied complexes. The experiments with the plasmid DNA reveal that at the physiological levels of hydrogen peroxide the Cu(II)-viomycin complex is more aggressive against DNA than uncomplexed metal ions. Moreover, the degradation of DNA by viomycin can be carried out without the presence of transition metal ions. In the studies of antigenomic delta ribozyme catalytic activity, viomycin and its complex are shown to modulate the ribozyme functioning. The molecular modelling approach allows the indication of two different locations of viomycin binding sites to the ribozyme

Impact of Cu2+ ions on the structure of colistin and cell-free system nucleic acid degradation

Colistin and transition metal ions are commonly used as feed additives for livestock animals. This work presents the results of an analysis of combined potentiometric and spectroscopic (UV-vis, EPR, CD, NMR) data which lead to conclude that colistin is able to effectively chelate copper(II) ions. In cell-free system the oxidative activity of the complex manifests itself in the plasmid DNA destruction with simultaneous generation of reactive (OH)-O-center dot species, when accompanied by hydrogen peroxide or ascorbic acid. The degradation of RNA occurs most likely via a hydrolytic mechanism not only for complexed compound but also colistin alone. Therefore, huge amounts of the used antibiotic for nontherapeutic purposes might have a potential influence on livestock health. (C) 2015 Elsevier Inc. All rights reserved

Zn(II)-alloferon complexes – Similar sequence, different coordination modes, no antibacterial activity

Often, in the search for a highly defined scientific phenomenon, a different one becomes apparent. This was also the case of this work, in the scope of which we planned to search for metal-enhanced, novel antibacterial/antifungal compounds. Instead, we denied the existence of such and revealed the details of the bioinorganic chemistry of Zn(II)-alloferon complexes. Zinc(II) complexes of alloferon 1 and 2, ligands with a sequential difference of one amino acid only, show a substantially different coordination pattern at physiological pH. In the case of Zn(II)-alloferon 1 species, a histamine-like binding mode is observed (N-terminal amine and imidazole of His-1) and the coordination sphere is completed with the imidazole nitrogens of His-6 and His-9; His-12 is not involved in binding. In the case of Zn(II)-alloferon 2, the N-terminal amine and all the three imidazoles present in the sequence participate in the coordination, however, with the chemical shift of His-5 being less affected than those of other imidazoles. The histamine-like binding in Zn(II)-alloferon 1 complex strongly enhances its thermodynamic stability in comparison to the His-1 lacking alloferon 2 analogue. Despite previous reports on the antibacterial and antifungal activity of alloferon 1, no such activity was detected, neither for alloferon 1 and 2 nor for their Zn(II) complexes