DIETHYLSTILBESTROL-DNA INTERACTION STUDIED BY FOURIER-TRANSFORM INFRARED AND RAMAN-SPECTROSCOPY

The interaction of diethylstilbestrol (DES) with calf thymus DNA was i nvestigated at physiological pH with drug/DNA (phosphate) molar ratios (r) of 1:40, 1:20, 1:10, 1:4, 1:2, and 1. Fourier transform infrared and laser Raman difference spectroscopy were used to establish cor rel ations between spectral changes and drug binding mode, sequence select ivity, DNA conformation, and structural properties of DES . DNA comple xes in aqueous solution. Spectroscopic results indicated that DES is a weak intercalator with affinity for A-T-rich regions. It is also a gr oove binder with a major interaction with the thymine O-2 atom, At low drug concentration (r = 1:40), the A-T-rich region is the main target of drug intercalation, while at a higher drug content (r > 1:5), exte rnal binding to the G-C bases also occurs with a partial helix destabi lization. Evidence for this comes from the spectral alterations of the A-T vibrational frequencies at 1661 cm(-1) (Raman) and 1663 and 1609 cm(-1) (IR) and of the G-C vibrations at 1581 and 1491 cm(-1) (Raman) and 1717 and 1492 cm(-1) (TR), Drug intercalation leads to a major red uction of B-DNA structure in favor of A-DNA.