Thermodynamic study of interactions of distamycin A in chromatin rat liver nuclei in the presence of polyaminesстатья
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Дата последнего поиска статьи во внешних источниках: 6 декабря 2018 г.
Аннотация:—We studied the thermodynamics of melting of isolated rat liver nuclei with different degrees of chromatin condensation determined by the concentration of polyamines (PA) and the solution ionic strength, as well as the effect of theantibiotic distamycin A (DM) on melting. Differential scanning calorimetry (DSC) profiles of nuclear preparations contained three peaks that reflected melting of three main chromatin domains. The number of peaks did not depend on thedegree of condensation; however, nuclei with more condensed chromatin had a higher total enthalpy. DM stabilized peaksII and III corresponding to the melting of relaxed and topologically strained DNA, respectively, but destabilized peak I corresponding to the melting of nucleosome core histones. At the saturating concentration (DM/DNA molar ratio = 0.1), DMincreased Tm of peaks II and III by ~5°C and decreased Tm of peak I by ~2.5°C. Based on the dependence of ΔH on DMconcentration, we established that at low DM/DNA ratio (0.03), when DM interacted predominantly with ATrich DNAregions, the enthalpy of peak II decreased in parallel with the increase in the enthalpy of peak III, which indicated that DMinduces structural transitions in the nuclear chromatin associated with the increase in torsional stress in DNA. An increasein free energy under saturation conditions was equal to the change in the free energy of DM interaction with DNA.However, the increase in the enthalpy of melting of the nuclei in the presence of DM was much greater than the enthalpyof titration of nuclei with DM. This indicates a significant increase in the strength of interaction between the two DNAstrands apparently due, among other things, to changes in the torsional stress of DNA in the nuclei. Titration of the nucleiwith increasing PA concentrations resulted in the decrease in the number of DMbinding sites and the nonmonotonousdependence of the enthalpy and entropy contribution to the binding free energy on the PA content. We suggested that theobserved differences in the thermodynamic parameters were due to the different width of the minor groove in the nuclearchromatin DNA, which depends on PA concentration.