NMR Characterization of a DNA Duplex Containing the Major Acrolein-derived Deoxyguanosine Adduct γ-OH-1,-N²-Propano-2′ -deoxyguanosine

The environmental and endogenous mutagen acrolein reacts with cellular DNA to produce several isomeric 1,N²-propanodeoxyguanosine adducts. High resolution NMR spectroscopy was used to establish the structural features of the major acrolein-derived adduct, γ-OH-1,N²-propano-2′ -deoxyguanosine. In aqueous solution, this adduct was shown to assume a ring-closed form. In contrast, when γ-OH-1,N²-propano-2′ -deoxyguanosine pairs with dC at the center of an 11-mer oligodeoxynucleotide duplex, the exocyclic ring opens, enabling the modified base to participate in a standard Watson-Crick base pairing alignment. Analysis of the duplex spectra reveals a regular right-handed helical structure with all residues adopting an anti orientation around the glycosidic torsion angle and Watson-Crick alignments for all base pairs. We conclude from this study that formation of duplex DNA triggers the hydrolytic conversion of γ-OH-1,N ²-propano-2′-deoxyguanosine to an open chain form, a structure that facilitates pairing with dC during DNA replication and accounts for the surprising lack of mutagenicity associated with this DNA adduct.