Divalent cations are dispensable for binding to DNA of a novel positively charged olivomycin A derivative
| Autor: | Anna N. Tevyashova, Anna K. Shchyolkina, Alexander A. Shtil, A. D. Beniaminov, O. K. Mamaeva, Lyubov G. Dezhenkova, Dmitry N. Kaluzhny |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Circular dichroism Luminescence Stereochemistry Chemical physics Agarose Gel Electrophoresis chemistry.chemical_element lcsh:Medicine Research and Analysis Methods Physical Chemistry Fluorescence Divalent 03 medical and health sciences chemistry.chemical_compound Electrophoretic Techniques Cations Static electricity Binding site lcsh:Science Molecular Biology Techniques Molecular Biology Free Energy Gel Electrophoresis chemistry.chemical_classification Ions Multidisciplinary 030102 biochemistry & molecular biology Chemical Bonding Magnesium Physics Electromagnetic Radiation lcsh:R Biology and Life Sciences Dimers (Chemical physics) Electrophoresis Chemistry 030104 developmental biology chemistry Physical Sciences Enzyme Immobilization Thermodynamics lcsh:Q Electrostatic Bonding DNA Research Article Ionic Binding Method |
| Zdroj: | PLoS ONE PLoS ONE, Vol 13, Iss 2, p e0191923 (2018) |
| ISSN: | 1932-6203 |
| Popis: | The current model of binding of the antitumor antibiotic olivomycin A (1) to GC-rich DNA regions presumes that coordination of the magnesium divalent cation with drug dimers is necessary for binding of 1 into the minor groove of the DNA duplex. Previously we have synthesized the derivatives of 1 termed 'short acid' (2) and its N,N-dimethylaminoethylamide (3). The latter compound demonstrated an improved tolerance in vivo compared to 1 and good therapeutic potency in animal models. We herein report that compound 3 is able to form stable complexes with DNA in the absence of Mg2+, in striking contrast to 1 whose binding to the DNA absolutely requires Mg2+. The mode of binding of 3 to DNA is similar in the presence or absence of Mg2+ as determined by circular dichroism. The affinity to DNA of 3 in Mg2+-free solution was similar to that of 1 or 3 in the presence of Mg2+ at low ionic strength. Non-electrostatic contributions to total free energy of binding of 1 and 3 to DNA were comparable for Mg2+-free complexes. Our data strongly suggest that electrostatic interaction of the positively charged 3 can compensate for the absence of divalent ions in complexes with DNA. This new property of the olivomycin A derivative expands the mechanistic knowledge of the modes of interaction with DNA of small molecular weight drug candidates. |
| Databáze: | OpenAIRE |
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