RNA-DIETHYLSTILBESTROL INTERACTION STUDIED BY FOURIER-TRANSFORM INFRARED DIFFERENCE SPECTROSCOPY

Diethylstilbestrol: (DES), a synthetic estrogen, is known to be a carc inogen in human and in animals. This study was designed to examine the interaction of DES with yeast RNA in aqueous solution at physiologica l pH with drug/RNA-phosphate (P) molar ratios of 1/80, 1/40, 1/20, 1/1 0, 1/4, and 1/2. Fourier transform infrared (FTIR) difference spectros copy was used to determine the drug binding mode, the binding constant , the sequence selectivity, and RNA secondary structure in the RNA.DES complexes. Spectroscopic evidence showed that at low drug concentrati on (1/80 and 1/40), DES is intercalating through both Gua-Cyt and Ade- Urd base pairs with minor interaction with the backbone PO2 group (ext ernal binding). The calculated binding constant of K similar to 8.5 x 10(4) M(-1) at a drug concentration of 3.12 x 10(-4) M shows that DES is a weaker intercalator than those of the methylene blue, acridine or ange, and ethidium bromide. At high drug content (r > 1/40, where r re presents the DES/RNA-phosphate molar ratio), a partial helix destabili zation occurs with no alteration of RNA conformation upon drug complex ation. However, a comparison with DNA.DES complexes showed that drug i ntercalation causes major reduction of the B-DNA structure in favor of A-DNA with no participation of the backbone PO2 group in the DES.DNA complexation.