Artigos
URI permanente para esta coleçãohttps://locus.ufv.br/handle/123456789/11797
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Item Doxorubicin hinders DNA condensation promoted by the protein bovine serum albumin (BSA)(Biopolymers, 2017-10-23) Lima, C. H. M.; Paula, H. M. C. de; Silva, L. H. M. da; Rocha, M. S.In this work, we have studied the interaction between the anticancer drug doxorubicin (doxo) and condensed DNA, using optical tweezers. To perform this task, we use the protein bovine serum albumin (BSA) in the working buffer to mimic two key conditions present in the real intracellular environment: the condensed state of the DNA and the abundant presence of charged macromolecules in the surrounding medium. In particular, we have found that, when doxo is previously intercalated in disperse DNA, the drug hinders the DNA condensation process upon the addition of BSA in the buffer. On the other hand, when bare DNA is firstly condensed by BSA, doxo is capable to intercalate and to unfold the DNA condensates at relatively high concentrations. In addition, a specific interaction between BSA and doxo was verified, which significantly changes the chemical equilibrium of the DNA–doxo interaction. Finally, the presence of BSA in the buffer stabilizes the double-helix structure of the DNA–doxo complexes, preventing partial DNA denaturation induced by the stretching forces.Item DNA-doxorubicin interaction: New insights and peculiarities(Biopolymers, 2016-10-05) Silva, E. F.; Bazoni, R. F.; Ramos, E. B.; Rocha, M. S.We have investigated the interaction of the DNA molecule with the anticancer drug doxorubicin (doxo) by using three different experimental techniques: single molecule stretching, single molecule imaging, and dynamic light scattering. Such techniques allowed us to get new insights on the mechanical behavior of the DNA-doxo complexes as well as on the physical chemistry of the interaction. First, the contour length data obtained from single molecule stretching were used to extract the physicochemical parameters of the DNA-doxo interaction under different buffer conditions. This analysis has proven that the physical chemistry of such interaction can be modulated by changing the ionic strength of the surrounding buffer. In particular we have found that at low ionc strengths doxo interacts with DNA by simple intercalation (no aggregation) and/or by forming bound dimers. For high ionic strengths, otherwise, doxo-doxo self-association is enhanced, giving rise to the formation of bound doxo aggregates composed by 3 to 4 molecules along the double-helix. On the other hand, the results obtained for the persistence length of the DNA-doxo complexes is strongly force-dependent, presenting different behaviors when measured with stretching or non-stretching techniques.