Nmr spektroskopske študije interakcij kovinskih ionov z dnk (slovene)

Our studies are directed towards the examination of the binding characteristics of cations to nucleic acids in order to understand the formation of specific binding sites for mono and divalent metal ions and to be able to explain how the binding of metal ions stabilises high ordered structures (e.g. G-quadruplexes) or may for example result in the conformational changes, which are important for activity of metal ion complexes as drugs (e.g. Pt complexes with anticancer activity). Multinuclear NMR studies of the interactions of metal ions with DNA constituents provide a quantitative insight into the electrostatic vs. more coordinative nature of the interactions through the evaluation of the thermodynamics of North (roughly C3''-endo) = South (roughly C2''-endo) pseudorotational equilibrium in relation to the conformational equilibria along sugar-phosphate backbone. The interaction or binding of metal ions to nitrogen atom of the heterocycle is directly responsible for the redistribution of pi-electron density of the heterocyclic moiety, which is transferred to the drive of North = South pseudorotational equilibrium via anomeric effect and in this way indirectly influencing the local folding and thus the structure of nucleic acids. The analysis of temperature-dependent 3JHH coupling constants enabled the quantification of the strengthening of the anomeric effect in our model systems, which determines the population of N-type conformers with the pseudoaxially oriented nucleobase. The analysis of heteronuclear 3JHP and 3JCP coupling constants has established the correlation between the conformational changes of the North = South pseudorotational equilibrium upon M2+ interactions and the conformational equlibria across glycosyl bond and torsion angles beta, gamma and epsilon. The structural and conformational studies of potential antitumor and antiviral agents provide the basis for the formulation of the correlation between their structure and activity.