Investigação das interações da molécula de DNA com elementos terras-raras

Abstract

The oxides of Europium (Eu2O3), Erbium (Er2O3), Ytterbium (Yb2O3) and Neodymium (Nd2O3) were used to evaluate the affinity of these rare earth elements in the interaction with double stranded DNA molecules. To perform the study, we used single-molecule force spectroscopy with optical tweezers and gel electrophoresis assays. Force spectroscopy assays show that all four rare earths studied showed a strong interaction with double-stranded DNA. The interaction between Eu2O3 and the DNA molecule is independent of the ionic strength used in the surrounding environment Eu2O3 tends to bind cooperatively, forming clusters of molecules (∼ 3) and exhibits a high equilibrium association binding constant of the order of 105 M−1 . Furthermore, gel electrophoresis confirms the weak electrostatic character of the interaction and explicitly shows that Eu2O3 does not interfere with drug intercalation in the double helix. Er2O3 has a strong interaction with double-stranded DNA, strongly condensing it for concentrations above 0.04 µM, leading to a 50% reduction in its contour length in a concentration of 0.1 µM of the oxide. Er2O3's ability to compact the structure of the DNA molecule makes it promising for applicability in gene therapy, for example. We have seen that Er2O3, Yb2O3 and Nd2O3 prevent the force indiced melting of the double helix chain, in addition to having high affinity with the molecule, as they have an equilibrium association binding constant of the order of 106 M-1 to 107 M-1 . For Yb2O3 and Nd2O3, we observed that in addition to high affinity, they are also cooperative, indicating that when they bind to the DNA molecule, they collaborate with the next binding that will happen, forming clusters of molecules similar to Eu2O3. The cooperativity is measured by the Hill coefficient, which is obtained through the persistence length as a function of the concentration of the metals studied separately. Such results demonstrate the potential of rare earths to interact with nucleic acids and strongly suggest that these rare earth elements can be considered for the design of new metal-based anticancer drugs.