Spectroscopic and calorimetric studies on the binding of alkaloids berberine, palmatine and coralyne to double stranded RNA polynucleotides.

The interaction of two natural protoberberine plant alkaloids berberine and palmatine and a synthetic derivative coralyne to three double stranded ribonucleic acids, poly(A). poly(U), poly(I).poly(C) and poly(C).poly(G) was studied using various biophysical techniques. Absorbance and fluorescence studies showed that the alkaloids bound cooperatively to these RNAs with the binding affinities of the order 10(4) M(-1). Circular dichroic results suggested that the conformation of poly(A). poly(U) was perturbed by all the three alkaloids, that of poly(I).poly(C) by coralyne only and that of poly(C).poly(G) by none. Fluorescence quenching studies gave evidence for partial intercalation of berberine and palmatine and complete intercalation of coralyne to these RNA duplexes. Isothermal titration calorimetric studies revealed that the binding was characterized by negative enthalpy and positive entropy changes and the affinity constants derived were in agreement with the overall binding affinity from spectral data. The binding of all the three alkaloids considerably stabilized the melting of poly(A). poly(U) and poly(I).poly(C) and the binding data evaluated from the melting data were in agreement with that obtained from other techniques. The overall binding affinity of the alkaloids to these double stranded RNAs varied in the order, berberine = palmatine < coralyne. The temperature dependence of the enthalpy changes afforded large negative values of heat capacity changes for the binding of palmatine and coralyne to poly(A).poly(U) and of coralyne to poly(I).poly(C), suggesting substantial hydrophobic contribution in the binding process. Further, enthalpy-entropy compensation was also seen in almost all the systems that showed binding. These results further advance our understanding on the binding of small molecules that are specific binders to double stranded RNA sequences.