Targeting RNA by Small Molecules: Comparative Structural and Thermodynamic Aspects of Aristololactam-β-D-glucoside and Daunomycin Binding to tRNAphe

BackgroundInteraction of aristololactam-β-D-glucoside and daunomycin with tRNAphe was investigated using various biophysical techniques. Methodology/Principal FindingsAbsorption and fluorescence studies revealed that both the compounds bind tRNAphe non-cooperatively. The binding of daunomycin was about one order of magnitude higher than that of aristololactam-β-D-glucoside. Stronger binding of the former was also inferred from fluorescence quenching data, quantum efficiency values and circular dichroic results. Results from isothermal titration calorimetry experiments suggested that the binding of both compounds was predominantly entropy driven with a smaller but favorable enthalpy term that increased with temperature. A large favorable electrostatic contribution to the binding of daunomycin to tRNAphe was revealed from salt dependence data and the dissection of the free energy values. The electrostatic component to the free energy change for aristololactam-β-D-glucoside-tRNAphe interaction was smaller than that of daunomycin. This was also inferred from the slope of log K versus [Na+] plots. Both compounds enhanced the thermal stability of tRNAphe. The small heat capacity changes of -47 and -99 cal/mol K, respectively, observed for aristololactam-β-D-glucoside and daunomycin, and the observed enthalpy-entropy compensation phenomenon confirmed the involvement of multiple weak noncovalent interactions. Molecular aspects of the interaction have been revealed. Conclusions/SignificanceThis study presents the structural and eneregetic aspects of the binding of aristololactam-β-D-glucoside and daunomycin to tRNAphe.