Formylamino pyrimidines (Fapy) are the product of imidazole ring opening of purines. Along with 8-oxoguanine they are the most abundant DNA lesions resulting from oxidative damage in on DNA. In order to characterize the effect of a Fapy-dG lesion on DNA structure we prepared an undecanucleotide duplex bearing a carba-Fapy-dG residue opposite cytosine and performed its NMR characterization. Carba-Fapy-dG has the deoxyribose ring replaced with a cyclopentane isoster, modification that suppress spontaneous anomerisation.

Our data show that incorporation of the beta-carbaFapy residue induces no major perturbations on the normal B-type DNA helix. The Fapy base is stacked into a helix and forms Watson-Crick type hydrogen bonds with its partner cytosine. Normal nOe connectivities are conserved throughout the backbone of both unmodified and modified DNA strands, the only break being associated with the absence of H-8. The formyl group of Fapy resides in the major groove of the helix where a formyl proton makes no strong nOe contacts with protons of adjacent nucleotides.