Aflatoxin B1 (AFB1) is the predominant mutagenic fungal metabolite produced by Aspergillus flavus. The genotoxic metabolic product, AFB1 epoxide, alkylates DNA regioselectively at N7-dG.  The initially formed N7-dG adduct may subsequently rearrange to a N7-dG formamidopyrimidine (FAPY) derivative. In DNA, the AFB1-FAPY derivative equilibrates between two rotamers, E and Z, which are differentiated by the rotation of the formyl bond. Using NMR, we examine the hypothesis that the structure of the AFB1-FAPY modified dG is dependent on the 3'-neighbor nucleotides. The 5'-XA-3' and 5'-XT-3' sequences (X= AFB1-FAPY lesion) were used to compare the structure of AFB1-FAPY modified dG. The 5'-XA-3' sequence predominately existed as the b anomer and the E rotamer about the formyl bond, whereas the 5'-XT-3' sequence predominately existed as the b anomer and Z rotamer.  The 1D experiment showed multiple species for both sequences at the higher temperature. This might be attributed to the co-existence of E and Z conformations of the formamide moiety.  Supported by NIH grant R01 CA-55678 (M.P.S.). Funding for NMR was supplied by NIH grants S10 RR-05805, S10 RR-025677 and NSF Grant DBI 0922862, the latter funded by the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).

Sequence-dependent structural perturbations induced by the �-anomer of the aflatoxin B<sub>1</sub> formamidopyrimidine (FAPY) adduct in DNA

246th National Meeting (2013)

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Sequence-dependent structural perturbations induced by the �-anomer of the aflatoxin B1 formamidopyrimidine (FAPY) adduct in DNA

Sequence-dependent structural perturbations induced by the �-anomer of the aflatoxin B₁ formamidopyrimidine (FAPY) adduct in DNA