Study on the interaction of glycyrrhizin and glycyrrhetinic acid with RNA

Glycyrrhizin is a well known pharmacologically bioactive natural glycoside. Glycyrrhizin (GL) has been widely used as a therapeutic agent for chronic active liver diseases. Glycyrrhetinic acid is an aglycone and an active metabolite of glycyrrhizin. This study is the first attempt to locate the binding sites of glycyrrhizin and glycyrrhetinic acid to RNA. The effect of the ligand complexation on RNA aggregation was investigated in aqueous solution at physiological conditions, using constant RNA concentration (6.25 mM) and various ligand/polynucleotide (phosphate) ratios of 1/280, 1/240, 1/120, 1/80, 1/40, 1/20, 1/10, 1/5, 1/2 and 1/1. Fourier transform infrared (FTIR) and UV–Visible spectroscopic methods as well as molecular modeling were used to determine the ligand binding modes, the binding constants, and the stability of ligands–RNA complexes in aqueous solution. Spectroscopic evidence showed that glycyrrhizin and glycyrrhetinic acid bind RNA via G–C and A–U base pairs as well as the backbone phosphate group with overall binding constants of KGL–RNA = 3.03 × 103 M−1, KGA–RNA = 2.71 × 103 M−1. The affinity of ligands–RNA binding is in the order of glycyrrhizin > glycyrrhetinic acid. RNA remains in the A-family structure, while biopolymer aggregation occurred at high triterpenoid concentrations.

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► Glycyrrhizin and glycyrrhetinic acid bind RNA via polypeptide polar groups.
► Glycyrrhizin and glycyrrhetinic acid mainly interact with G–C and A–U base pairs as well as the backbone phosphate group.
► The affinity of ligands–RNA binding is in the order of glycyrrhizin > glycyrrhetinic acid.
► RNA remains in the A-family structure, while biopolymer aggregation occurred at high triterpenoid concentrations.