Binding of the plant alkaloid aristololactam-β-D-glucoside and antitumor antibiotic daunomycin to single stranded polyribonucleotides

Background: Interaction of the plant alkaloid aristololactam-beta-D-glucoside and the antitumor drug daunomycin with single stranded RNAs poly(G), poly(I), poly(C) and poly(U) has been investigated. Methods: Biophysical techniques of absorption, fluorescence, competition dialysis, circular dichroism, and micro-calorimetry have been used. Results: Absorption and fluorescence studies have revealed noncooperative binding of ADG and DAN to the single stranded RNAs. The binding affinity of ADG varied as poly(G) > poly(I) > >poly(C) > poly(U). The affinity of DAN was one order higher than that of ADG and varied as poly(G) > poly(I) > poly(U) > poly(C). This binding preference was further confirmed by competition dialysis assay. The thermodynamics of the binding was characterised to be favourable entropy and enthalpic terms but their contributions were different for different systems. The major non-polyelectrolytic contribution to the binding revealed from salt dependent data appears to be arising mostly from stacking of DAN and ADG molecules with the bases leading to partial intercalation to single stranded RNA structures. Small negative heat capacity values have been observed in all the four cases. Conclusions: This study presents the comparative structural and thermodynamic profiles of the binding of aristololactam-beta-D-glucoside and daunomycin to single stranded polyribonucleotides. General significance: These results suggest strong, specific but differential binding of these drug molecules to the single stranded RNAs and highlight the role of their structural differences in the interaction profile. (c) 2013 Elsevier B.V. All rights reserved.