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DNA Adducts With Chlorophyll and Chlorophyllin As Antimutagenic Agents

Synthesis, Stability, and Structural Features
  • Heidar-Ali Tajmir-Riahi
  • Jean-Francois Neault
  • Stavroula Diamantoglou
Part of the Methods In Molecular Biology™ book series (MIMB, volume 274)

Abstract

Porphyrins and their metal derivatives are strong DNA binders with association constants of 105 M −1 to 107 M −1. Some of these compounds have been used for radiation sensitization therapy of cancer and are targeted to interact with cellular DNA. Chlorophyll (CHL) and chlorophyllin (CHLN), a food-grade derivative of chlorophyll, the ubiquitous green plant pigment widely consumed by humans, are potent inhibitors of experimental carcinogenesis. The aim of this report was to examine the interaction of calf-thymus DNA with CHL and CHLN in aqueous solution at physiological pH, with pigment/DNA(phosphate) molar ratios (r) of 1/80 to 1/2. Fourier transform infrared (FTIR) difference spectroscopic method was used to determine the pigment binding mode, binding constant, sequence selectivity, DNA secondary structure and structural variations of the pigment-DNA complexes in aqueous solution.

Spectroscopic evidence showed that chlorophyll is an external DNA binder with no affinity toward DNA intercalation. CHL bindings are through the backbone PO2 group and the guanine N-7 site of the G-C base pair (major groove) with overall binding constant of K=1.13×104 M −1 CHLN binds DNA via intercalative mode into the G-C and A-T-rich regions with a minor perturbation of the backbone PO2 group with overall binding constant K=3.56×103 M −1. However, The CHL distributions are 60% with the backbone PO2 group and 20% with the G-C base pairs, whereas CHLN intercalation is 25% with A-T and 15% with G-C base pairs. A partial reduction of B-DNA structure in favor of A-DNA occurs upon CHL and CHLN complexation.

Key Words

DNA chlorophyllin chlorophyll antimutagen drug binding mode binding constant conformation FTIR spectroscopy helix stability 

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Copyright information

© Humana Press Inc., Totowa, NJ 2004

Authors and Affiliations

  • Heidar-Ali Tajmir-Riahi
    • 1
  • Jean-Francois Neault
    • 1
  • Stavroula Diamantoglou
    • 1
  1. 1.Département de Chimie-Bioloige (GREIB)Université du Québec à Trois-RivièresQuébecCanada

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