DNA - CHLOROPHYLLIN INTERACTION

Porphyrins and their metal derivatives are strong DNA binders with ass ociation constants of around 10(6) M-1. Some of these compounds have b een used for radiation sensitization therapy of cancer and are targete d to interact with cellular DNA. Chlorophyllin (CHLN), a food-grade de rivative of chlorophyll (CHL), the ubiquitous green plant pigment wide ly consumed by humans, is a potent inhibitor of experimental carcinoge nesis. The aim of this study was to examine the interaction of calf-th ymus DNA with chlorophyllin in aqueous solution at physiological pH, w ith CHLN/DNA (phosphate) molar ratios (r) of 1/80, 1/40, 1/20, 1/10 1/ 4, and 1/2. Fourier transform infrared (FTIR) difference spectroscopy was used to determine the CHLN binding mode, binding constant, sequenc e selectivity, DNA secondary structure, and structural variations of t he DNA-CHLN complexes in aqueous solution. Spectroscopic evidence show ed that at low pigment concentration (r = 1/80), CHLN binds DNA via in tercalative mode into the G-C and A-T-rich regions with a minor intera ction toward the backbone PO2 group (outside binding). At r > 1/80, a partial reduction of B-DNA structure in favor of A-DNA occurs upon dru g complexation. At high drug content (r > 1/20), a minor helix opening is observed. The calculated binding constant K = 3.56 x 10(3) M-1 sho ws chlorophyllin as a weak DNA intercalator. The DNA-chlorophyllin com plexation is rather different from that of the DNA- chlorophyll intera ction, in which chlorophyll binding is mainly through the backbone PO2 group with minor cation-base interaction (groove binding).