Abstract
Aflatoxins B1 and B2 intercalate with B-DNA, as demonstrated by NMR analysis of association with d(ATGCAT)2 and d(GCATGC)2, alteration of pBR322 electrophoretic mobility, and flow dichroism using linearly oriented calf thymus DNA. The less planar δ-lactone ring of aflatoxins G1 and G2 reduces DNA binding affinity by approximately one order of magnitude, but binding studies suggest that aflatoxins G1 and G2 also bind B-DNA by intercalation. At low DNA concentration, the number of adducts formed by either aflatoxin B1-8,9-epoxide or aflatoxin G1-9,10-epoxide is reduced with a concomitant increase in formation of the respective dihydrodiols, and the ratio of adducts formed by aflatoxin G1-9,10-epoxide to those formed by an equivalent concentration of aflatoxin B1-8,9-epoxide decreases. Reaction of aflatoxin B1-8,9-epoxide with d(ATCGAT)2 exhibits a limiting stoichiometry of 1:1 aflatoxin B1:d(ATCGAT)2. In contrast, reaction of aflatoxin B1-8,9-epoxide with d(ATGCAT)2 exhibits a limiting stoichiometry of 2:1 aflatoxin B1:d(ATGCAT)2. 1H NOE experiments, non-selective 1H T1 relaxation measurements, and 1H chemical shift perturbations demonstrate that in each case the aflatoxin moiety is intercalated above the 5’ face of the modified guanine. These data are consistent with an intercalated transition state complex between aflatoxin B1-8,9-epoxide and B-DNA.
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Stone, M.P., Gopalakrishnan, S., Raney, K.D., Raney, V.M., Byrd, S., Harris, T.M. (1990). Aflatoxin-DNA Binding and the Characterization of Aflatoxin B1-Oligodeoxynucleotide Adducts by 1H NMR Spectroscopy. In: Pullman, B., Jortner, J. (eds) Molecular Basis of Specificity in Nucleic Acid-Drug Interactions. The Jerusalem Symposia on Quantum Chemistry and Biochemistry, vol 23. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-3728-7_30
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DOI: https://doi.org/10.1007/978-94-011-3728-7_30
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