Cisplatin GG-crosslinks within single-stranded DNA: Origin of the preference for left-handed helicity

Monnet, Jordan; Kozelka, Jiřı́

doi:10.1016/j.jinorgbio.2012.05.015

Cited by 2 publications

(2 citation statements)

References 31 publications

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“…clarified and quantified various aspects of cisplatin's biochemistry, including the kinetics and 78 thermodynamics of aquation and binding to DNA and other biological molecules, and the 79 distortions induced in DNA on binding. 19,20,21,22,23 Similar studies of oxaliplatin and other 80 alternatives have been reported, illuminating the similarities and differences between 81 drugs. 24,25 Density functional theory (DFT) is the method of choice in almost all such studies, 82 offering an excellent balance between accuracy and computational time and effort required.…”

Section: Introduction 35mentioning

confidence: 68%

“…However, such methods are 85 typically applicable to a few hundred atoms with current computing, effectively limiting the 86 size of DNA fragment to just two base pairs. Molecular mechanics (MM) methods are 87 capable of describing much larger systems, and also to rapidly explore conformational 88 freedom as in the recent study of cisplatin-TGG adducts, 23 but to date parameters are 89 available only for cisplatin and oxaliplatin. 90…”

Section: Introduction 35mentioning

confidence: 99%

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Computational evidence for structural consequences of kiteplatin damage on DNA

et al. 2014

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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 (1)H-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.

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Section: Introduction 35mentioning

confidence: 68%

Section: Introduction 35mentioning

confidence: 99%

Computational evidence for structural consequences of kiteplatin damage on DNA

et al. 2014

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Molecular dynamics simulation and free energy analysis of the interaction of platinum-based anti-cancer drugs with DNA

Jalili

Maddah

Schofield

2016

J. Theor. Comput. Chem.

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Cisplatin and oxaliplatin are two widely-used anti-cancer drugs which covalently bind to a same location in DNA strands. Platinum agents make intrastrand and interstrand cross-links with the N7 atoms of guanine nucleotides which prevent DNA from polymerization by causing a distortion in the double helix. Molecular dynamics simulations and free energy calculations were carried out to investigate the binding of two platinum-based anti-cancer drugs with DNA. We compared the binding of these drugs which differ in their carrier ligands, and hence their potential interactions with DNA. When a platinum agent binds to nucleotides, it causes a high amount of deformation in DNA structure. To find the extent of deformation, torsion angles and base pair and groove parameters of DNA were considered. These parameters were compared with normal B-DNA which was considered as the undamaged DNA. The formation of hydrogen bonds between drugs and DNA nucleotides was examined in solution. It was shown that oxaliplatin forms more hydrogen bonds than cisplatin. Our results confirm that the structure of the platinated DNA rearranges significantly and cisplatin tries to deform DNA more than oxaliplatin. The binding free energies were also investigated to understand the affinities, types and the contributions of interactions between drugs and DNA. It was concluded that oxaliplatin tendency for binding to DNA is more than cisplatin in solvent environment. The binding free energy was calculated based on the MM/PBSA and MM/GBSA methods and the results of QM/MM calculations verified them.

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Cisplatin GG-crosslinks within single-stranded DNA: Origin of the preference for left-handed helicity

Cited by 2 publications

References 31 publications

Computational evidence for structural consequences of kiteplatin damage on DNA

Computational evidence for structural consequences of kiteplatin damage on DNA

Molecular dynamics simulation and free energy analysis of the interaction of platinum-based anti-cancer drugs with DNA

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