Modeling conformational dynamics of cisplatin and oxaliplatin adducts with DNA

Modeling conformational dynamics of cisplatin and oxaliplatin adducts with DNA Public Deposited

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Creator

Gong, Peng
- Affiliation: School of Medicine, UNC/NCSU Joint Department of Biomedical Engineering

Abstract

Cis-diamminedichloroplatinum(II) (cisplatin, CP) is a widely used anti-cancer agent. Its platinum analog (trans-R,R)1,2-diaminocyclohexaneoxalatoplatinum(II) (oxaliplatin, OX) is often effective in cisplatin resistant tumors and generally causes less mutation than CP. Although their carrier ligands are structurally distinct, CP and OX form the same types of adducts at the same sites on the DNA. Certain DNA regulatory proteins could distinguish CP-DNA adducts from OX-DNA adducts but the underlying mechanism is not clear currently. In this thesis, we utilized molecular dynamics computer simulation to study these two adducts and we found that DNA was more distorted on the 5' side of the adduct than the 3' side, CP adduct was oriented more towards the 5' side of the adduct and OX adduct more towards the 3' side and some significant differences were observed in the frequency distributions of DNA duplex helical parameters, which may provide an explanation to their distinct biological properties.

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