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

. 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 DN...

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Bibliographic Details
Published in:The European physical journal. E, Soft matter and biological physics Soft matter and biological physics, 2019-10, Vol.42 (10), p.130-130, Article 130
Main Authors: Lima, C. H. M., Caquito, J. M., de Oliveira, R. M., Rocha, M. S.
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemistry
Binding
Biological and Medical Physics
Biophysics
Cancer
Complex Fluids and Microfluidics
Complex Systems
Condensed matter physics
Deoxyribonucleic acid
DNA
DNA - chemistry
Intercalating Agents - chemistry
Isoquinolines - chemistry
Ligands
Mechanical properties
Nanotechnology
Optical Tweezers
Physics
Physics and Astronomy
Polymer Sciences
Regular Article
Single Molecule Imaging - methods
Soft and Granular Matter
Statistical models
Surfaces and Interfaces
Thin Films
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Summary:. 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
ISSN:1292-8941
1292-895X
DOI:10.1140/epje/i2019-11895-6