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Base- and sequence-dependent binding of aristololactam beta-D-glucoside to deoxyribonucleic acid
Authors:R Nandi  S Chakraborty  M Maiti
Institution:Indian Institute of Chemical Biology, Calcutta.
Abstract:The dependence on base-pair composition and sequence specificity of the (aristololactam beta-D-glucoside)-DNA interaction was examined by spectrophotometric, spectrofluorometric, spectropolarimetric, thermal melting, thermodynamic, and viscometric studies. Binding of this alkaloid to various natural and synthetic DNAs was dependent upon the base composition and sequences of DNA. The binding parameters obtained from spectrophotometric analysis, according to an excluded-site model, indicated a relatively high affinity of the alkaloid binding to GC-rich DNA and alternating GC polymer. This affinity was further evidenced by the quenching of fluorescence intensity, decrease in quantum yield, and perturbations in circular dichroic spectrum. The alkaloid stabilized all DNAs against thermal denaturation. The temperature dependence of the binding constants was used to estimate the thermodynamic parameters involved in the complex formation of the alkaloid with various DNAs. The negative enthalpy and entropy change increased with increasing GC content of DNA and also compensated one another to produce a relatively small Gibbs free energy change. Viscometric studies showed that in the strong binding region the increase of contour length of DNA depended strongly on its base composition and sequence of bases, being larger for GC-rich DNA and alternating GC polymer. On the basis of these observations, it is concluded that the alkaloid binds to DNA by a mechanism of intercalation and exhibits considerable specificity toward alternating GC polymer.
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