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Computational evidence for structural consequences of kiteplatin damage on DNA

Mutter, Shaun T., Margiotta, Nicola, Papadia, Paride and Platts, James Alexis 2015. Computational evidence for structural consequences of kiteplatin damage on DNA. Journal of Biological Inorganic Chemistry 20 (1) , p. 35. 10.1007/s00775-014-1207-5

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Advanced Research Computing @ Cardiff (ARCCA)
Chemistry
Subjects: Q Science > QD Chemistry
Publisher: SpringerLink
ISSN: 0949-8257
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 2014
Last Modified: 05 Jun 2017 07:16
URI: http://orca.cf.ac.uk/id/eprint/69110

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