caa a22 4500 605506876 CHVBK 20210128100629.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00775-014-1207-5 doi (NATIONALLICENCE)springer-10.1007/s00775-014-1207-5 Computational evidence for structural consequences of kiteplatin damage on DNA [Elektronische Daten] [Shaun Mutter, Nicola Margiotta, Paride Papadia, James Platts] The reaction of the potential anticancer drug kiteplatin, cis-[PtCl2(cis-1,4-DACH)], with oligomers of single- and double-stranded DNA ranging from 2 to 12 base pairs in length was performed as a model for DNA interaction. The potential for conformational flexibility of single-stranded adducts was examined with density functional theory (DFT) and compared with data from 1H-NMR 1D and 2D spectroscopy. This indicates the presence of multiple conformations of an adduct with d(GpG), but only one form of the adduct with d(TGGT). The importance of a suitable theoretical model, and in particular basis set, in reproducing experimental data is demonstrated. The DFT theoretical model was extended to platinated base pair step (GG/CC), allowing a comparison to the related compounds cisplatin and oxaliplatin. Adducts of kiteplatin with larger fragments of double-stranded DNA, including tetramer, octamer, and dodecamer, were studied theoretically using hybrid quantum mechanics/molecular mechanics methods. Structural parameters of all the base-paired models were evaluated and binding energies calculated in gas phase and in solution; these are compared across the series and also with the related complexes cisplatin and oxaliplatin, thus revealing insights into how kiteplatin binds to DNA and similarities and differences between this and related compounds. Graphical Abstract: SBIC, 2014 Cisplatin nationallicence Kiteplatin nationallicence Oxaliplatin nationallicence DNA structure nationallicence DFT nationallicence QM/MM nationallicence Mutter Shaun School of Chemistry, Cardiff University, Park Place, CF10 3AT, Cardiff, UK aut Margiotta Nicola Department of Chemistry, University of Bari Aldo Moro, Via E. Orabona 4, 70125, Bari, Italy aut Papadia Paride Department of Biotechnology and Environmental Sciences, University of Salento, via Monteroni, 73100, Lecce, Italy aut Platts James School of Chemistry, Cardiff University, Park Place, CF10 3AT, Cardiff, UK aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/1(2015-01-01), 35-48 0949-8257 20:1<35 2015 20 775 https://doi.org/10.1007/s00775-014-1207-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-014-1207-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mutter Shaun School of Chemistry, Cardiff University, Park Place, CF10 3AT, Cardiff, UK aut NATIONALLICENCE 700 1- Margiotta Nicola Department of Chemistry, University of Bari Aldo Moro, Via E. Orabona 4, 70125, Bari, Italy aut NATIONALLICENCE 700 1- Papadia Paride Department of Biotechnology and Environmental Sciences, University of Salento, via Monteroni, 73100, Lecce, Italy aut NATIONALLICENCE 700 1- Platts James School of Chemistry, Cardiff University, Park Place, CF10 3AT, Cardiff, UK aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/1(2015-01-01), 35-48 0949-8257 20:1<35 2015 20 775