Oxaliplatin and its enantiomer induce different condensation dynamics of single DNA molecules

PLoS One. 2013 Aug 12;8(8):e71556. doi: 10.1371/journal.pone.0071556. eCollection 2013.

Abstract

The interactions of DNA with oxaliplatin (Pt(R,R-DACH)) or its enantiomer (Pt(S,S-DACH)) were investigated using magnetic tweezers and atomic force microscope. In the process of DNA condensation induced by Pt-DACH, only diadducts and micro-loops are formed at low Pt-DACH concentrations, while at high Pt-DACH concentrations, besides the diadducts and micro-loops, long-range cross-links are also formed. The diadduct formation rate of Pt(R,R-DACH) is higher than that of Pt(S,S-DACH). However, the proportions of micro-loops and long-range cross-links for Pt(S,S-DACH) are higher than those for Pt(R,R-DACH). We propose a model to explain these differences between the effect of Pt(R,R-DACH) and that of Pt(S,S-DACH) on DNA condensation. The study has strong implications for the understanding of the effect of chirality on the interaction between Pt-DACH and DNA and the kinetics of DNA condensation induced by platinum complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry*
  • DNA / drug effects
  • Models, Chemical
  • Molecular Structure
  • Organoplatinum Compounds / chemistry*
  • Organoplatinum Compounds / pharmacology
  • Oxaliplatin

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • DNA

Grants and funding

This work was supported by the National Natural Science Foundation of China (Grant 11274374) and the National Basic Research Program of China (973 Program) (Grant 2009CB930704). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.