Study on the interaction of homoisoflavonoids with RNA

Abstract

Homoisoflavonoids (3-benzylidene-4-chromanones) are isomers of flavonoids and exhibit different biological activities because of hydroxyl groups attaching to different positions. This study is the first attempt to locate the binding sites of four synthetic homoisoflavonoids: (E)-3-(3,4-dihydroxybenzylidene)-7-methoxychroman-4-one (BMC), (E)-3-(3,4-dihydroxybenzylidene)-7-propoxychroman-4-one (BPC), (E)-3-(4-hydroxybenzylidene)-7-methoxychroman-4-one (HBMC) and (E) 3-(4-hydroxybenzylidene)-chroman-4-one (HBC) to RNA. The effect of the ligand complexation on RNA aggregation was investigated in aqueous solution at physiological conditions, using constant RNA concentration (6.25mM) and various ligand/polynucleotide (phosphate) ratios of 1/120, 1/80, 1/40, 1/20, 1/10 and 1/5. Fourier transform infrared (FTIR) and UV–Visible spectroscopic methods were used to determine the ligand binding modes, the binding constants, and the stability of ligand–RNA complexes in aqueous solution. Spectroscopic evidence showed external binding of homoisoflavonoids to RNA duplex with overall binding constants of KBMC–RNA=1.06(±0.09)×104M−1, KBPC-RNA=1.11(±0.15)×104M−1, KHBC-RNA=3.82(±0.09)×103M−1 and KHBMC–RNA=5.82(±0.04)×103M−1. The affinity of homoisoflavonoid–RNA binding is in the order of BPC>BMC>HBMC>HBC. No biopolymer secondary structural changes were observed upon homoisoflavonoids interaction and RNA remains in the A-family structure in these complexes.