A theory of mode of act ion of Glycyrrhizin and Glycyrrhetinic Acid as D NA and RNA binding agents using automated flexi ble ligand docking

Glycyrrhizin is a well-known pharmaco logically bioactive natural glycoside. Glycyrrhizin (GL) has been widely used as a therapeutic ag ent for chronic active liver dis eases. Glycyrrhetinic acid (GA) is a n aglycone and an active metabolite of Glycyrrhizin. In this study Fourie r transform infrared (FTIR) and UV–visibl e spectrosc opic metho ds were used to determ ine the ligand binding modes, the binding cons tants, and t he stability of ligands – DNA, –RNA complexes in aqueous solution. S pectroscopic evidence showed that GL and GA bind DNA and RNA v ia G and A–T (A–U) base pairs as well as the backbone phosphate group with overall bind ing constan ts of KGL– DNA=۵.۷x۱۰ ۳ M-۱ (ǻGbinding= -۵.۱۲ kcal/mol), KGA– DNA=۵.۱x۱۰۳ M-۱ (ǻGbinding= -۵.۰۶ kcal/mol), KG L–RNA=۳.۰۳×۱۰۳ M-۱ (ǻGbinding= -۴.۷۴ kcal/m ol) and KG A–RNA=۲.۷۱×۱۰۳ M-۱ ( ǻGbinding= -۴ .۶۷ kcal/m ol). The affinity of ligands– DNA and –RNA binding is i n the order o f GL > GA. DNA rem ains in the B -family stru cture and RNA remain s in the A-family structure, while b iopolymer aggregation occurred at high ligand concentrations [۱, ۲]. We docked GL and GA onto the oligonucleoti de extracted from the crystal structures. For eve ry individu al model, the correlatio n between calculated binding and e xperimental values wer e analyzed to come acr oss most satisfying mod el. To determine the pr eferred binding sites on DNA and RNA.

کلیدواژه ها:

Dock ing ، DNA ، RNA ، Glycyrrhizin ، Glycyrrhetinic acid.