Interaction cisDDP with bases of DNA
Michal Zeizinger, Jaroslav V. Burda
Department of Chemical Physics and Optics, Faculty of Mathematics and Physics, Charles University, Prague, Ke Karlovu 3, Praha 2, 12116, Czech Republic
In previous study , two-bases (adenine-adenine, adenine-guanine and guanine-guanine) interactions with cisplatine were examined using ab initio methods. Current study represents further extention of that work including sugar-phosphate backbone which connects bases. Starting geometries of the studied systems (ApA, ApG and GpG) were based on X-ray Pt-GpG structure. The optimizations were performed using density functional Becke3LYP with 6-31G* basis; for platinum and phosphor pseudopotential description was used. Single-point second order Møller-Plesset perturbation theory (MP2) was used for the DFT-optimized structures. Then sugar-phosphate chain was removed and B-Pt-B bridged systems (B=A and G) were calculated (also at MP2/6-31G* level). Using these calculations, bond dissociation energies (BDE) of two bonds between Pt and N7 site at purine were determined for systems with and without sugar-phosphate string. Systems without sugar-phosphate string were also calculated at MP2/6-31+G* level, and BDE were determined for each Pt-B and Pt-NH3. These data were compared with energies from study .
It was shown that close correspondence can be found between Pt–N7 BDE’s for systems optimized without () and with (this work) sugar-phosphate backbone when these backbones are not considered. Similar comparison can be done within current model where the role of sugar-phosphate string can be elucidated. Analogous Pt–N7 BDE are additionally influenced mainly with coulomb interaction between negatively charged phosphate group and Pt cation. This causes an increase in BDE up to 40 kcal/mol in Pt-ApA complex.
 J.V. Burda, J. Leszczynski: Deformation of the DNA helix : The influence of cisplatin as relead by ab initio study of platinum(II) bridged DNA purine bases, J. Am. Chem. Soc., submitted
 P.M. Takahara, A.C. Rosenzweig, C.A. Frederick, S.J. Lippard, Crystal Structure of a Double-Stranded DNA Containing the Major Adduct of the Anticancer Drug Cisplatin, Nature, 377, pp. 649-652, 1995.