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Pixantrone anticancer drug as a DNA ligand: Depicting the mechanism of action at single molecule level

  • C. H. M. Lima
  • J. M. CaquitoJr.
  • R. M. de Oliveira
  • M. S. RochaEmail author
Regular Article

Abstract.

In this work we use single molecule force spectroscopy performed with optical tweezers in order to characterize the complexes formed between the anticancer drug Pixantrone (PIX) and the DNA molecule, at two very different ionic strengths. Firstly, the changes of the mechanical properties of the DNA-PIX complexes were studied as a function of the drug concentration in the sample. Then, a quenched-disorder statistical model of ligand binding was used in order to determine the physicochemical (binding) parameters of the DNA-PIX interaction. In particular, we have found that the PIX molecular mechanism of action involves intercalation into the double helix, followed by a significant compaction of the DNA molecule due to partial neutralization of the phosphate backbone. Finally, this scenario of interaction was quantitatively compared to that found for the related drug Mitoxantrone (MTX), which binds to DNA with a considerably higher equilibrium binding constant and promotes a much stronger DNA compaction. The comparison performed between the two drugs can bring clues to the development of new (and more efficient) related compounds.

Graphical abstract

Keywords

Living systems: Structure and Function 

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Copyright information

© EDP Sciences, Società Italiana di Fisica and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • C. H. M. Lima
    • 1
  • J. M. CaquitoJr.
    • 1
  • R. M. de Oliveira
    • 1
  • M. S. Rocha
    • 1
    Email author
  1. 1.Laboratório de Física Biológica, Departamento de FísicaUniversidade Federal de ViçosaViçosaBrazil

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