Interaction of aristololactam-β-D-glucoside and daunomycin with poly(A): Spectroscopic and calorimetric studies

The binding of two sugar containing antibiotics viz. aristololactam-β-D-glucoside and daunomycin with single and double stranded poly(A) was investigated by spectroscopic and calorimetric studies. The binding affinity of daunomycin to ss poly(A) was of the order of 106 M− 1 and that to ds poly(A) was of the order of 105 M− 1. Aristololactam-β-D-glucoside showed a relatively weaker binding with an affinity of the order of 104 M− 1 with both the conformations of poly(A). Fluorescence studies showed maximum quenching for daunomycin-ss poly(A) complexes. The binding constants calculated from fluorescence spectroscopy were in good agreement with that obtained from UV spectroscopy. Moderate perturbation of circular dichroic spectra of both the conformations of poly(A) in presence of these molecules with concomitant formation of prominent extrinsic CD bands in the 300-450 nm region further revealed the association. Isothermal titration calorimetry results showed an overall entropy driven binding in all the four systems though the entropy change was maximum in daunomycin-ss poly(A) binding. The binding affinity was also maximum for daunomycin-ss poly(A) and varied as daunomycin-ds poly(A)>aristololactam-β-D-glucoside-ds poly(A)>aristololactam-β-D-glucoside-ss poly(A). A 1:1 binding stoichiometry was observed in all the cases, as confirmed by Job plot analysis, indicating the interaction to consist of a single binding mode. Ferrocyanide quenching studies showed good stacking interaction in all cases but was best for daunomycin-ss poly(A) interaction. No self-structure formation was observed in poly(A) with both daunomycin and aristololactam-β-D-glucoside suggesting the hindrance of the sugar moiety for such structural organization.

Graphical AbstractResearch Highlights► Comparative studies on the interaction of the alkaloid aristololactam-β-D-glucoside and the anticancer agent daunomycin with single and double stranded poly(A) are presented. ► Daunomycin has higher binding affinity compared to aristololactam-β-D-glucoside to both structures of poly(A). ► Isothermal titration calorimetry showed an overall entropy driven binding in all the four systems though the entropy change was maximum in daunomycin-ss poly(A) binding. ► Evidence for good stacking interaction in all cases was obtained that was best for daunomycin-ss poly(A) interaction. ► No self structure formation in ss poly(A) was observed with both the compounds suggesting inhibition by the sugar moiety.