Investigations of the Binding of [Pt2(DTBPA)Cl2](II) and [Pt2(TPXA)Cl2](II) to DNA via Various Cross-Linking Modes

Abstract

We have constructed models for a series of platinum-DNA adducts that represent the binding of two agents, [Pt2(DTBPA)Cl2](II) and [Pt2(TPXA)Cl2](II), to DNA via inter- and intra-strand cross-linking, and carried out molecular dynamics simulations and DNA conformational dynamics calculations. The effects of trans- and cis-configurations of the centers of these di-nuclear platinum agents, and of different bridging linkers, have been investigated on the conformational distortions of platinum-DNA adducts formed via inter- and intra-strand cross-links. The results demonstrate that the DNA conformational distortions for the various platinum-DNA adducts with differing cross-linking modes are greatly influenced by the difference between the platinum-platinum distance for the platinum agent and the platinum-bound N7–N7 distance for the DNA molecule, and by the flexibility of the bridging linkers in the platinum agent. However, the effects of trans/cis-configurations of the platinum-centers on the DNA conformational distortions in the platinum-DNA adducts depend on the inter- and intra-strand cross-linking modes. In addition, we discuss the relevance of DNA base motions, including opening, shift and roll, to the changes in the parameters of the DNA major and minor grooves caused by binding of the platinum agent.

Investigation of thermodynamic and structural properties of drug delivery system based on carbon nanotubes as a carboplatin drug carrier by molecular dynamics simulations

“…SWCNTs were oxidized in acid to provide shortened nanotubes in carboxylate groups on ends and sidewalls [30][31][32][33][34]. Since DNA plays a key role in improving the therapeutic efficacy of platinum agents, computational research has been extensively conducted for a better understanding of how these agents react with DNA, especially cisplatin [35][36][37][38][39][40]. There is no report to evaluate theoretically the details of the interaction between the platinum agents and SWCNT as carrier.…”

Novel platinum-based anticancer drug: a complete vibrational study

“…Considering that (i) >75% hydrated DNA (B-DNA native conformation) is the main target of this kind of metal-based anticancer agents, (ii) the distance between two neighbouring bases that are perpendicular to the B-DNA main axis is ca 340 pm (base packing arrangement) and (iii) the average B-DNA double helix minor and major groove widths are 600 and 1160 pm, respectively, one can conclude that the possible conformers of the dinuclear platinum(II) chelate under study span the needed range of distances in order to establish either inter-or intrastrand crosslinks through DNA bases (preferably at the N7 atom of purines) (Lopes et al, 2012(Lopes et al, , 2013Yue et al, 2013).…”

DNA Structural Distortions Induced by a Monofunctional Trinuclear Platinum Complex with Various Cross-Links Using Molecular Dynamics Simulation

“…The restrained electrostatic potential (RESP) charges were computed at the B3LYP/LanL2DZ + 6-31G**level − using Gaussian09 . The force field parameters of MTPC involving Pt atoms were obtained in previous publications. − The rest of the parameters were taken from the general amber force field (gaff) using the ANTECHAMBER module of AMBER16…”