NMR characterization of a DNA duplex containing the major acrolein-deriveddeoxyguanosine adduct gamma-OH-1,N-2-propano-2 '-deoxyguanosine

The environmental and endogenous mutagen acrolein reacts with cellular DNA to produce several isomeric 1,N-2-propanodeoxyguanosine adducts. High resol ution NMR spectroscopy was used to establish the structural features of the major acrolein-derived adduct, gamma -OH-1,N-2-propano-2'-deoxyguanosine. In aqueous solution, this adduct was shown to assume a ring-closed form. In contrast, when gamma -OH-1,N-2-propano-2'-deoxyguanosine pairs with dC at the center of an 11-mer oligodeoxynucleotide duplex, the exocyclic ring ope ns, enabling the modified base to participate in a standard Watson-Crick ba se pairing alignment. Analysis of the duplex spectra reveals a regular righ t-handed helical structure with all residues adopting an anti orientation a round the glycosidic torsion angle and Watson-Crick alignments for all base pairs. We conclude from this study that formation of duplex DNA triggers t he hydrolytic conversion of gamma -OH-1,N-2-propano-2'-deoxyguanosine to an open chain form, a structure that facilitates pairing with dC during DNA r eplication and accounts for the surprising lack of mutagenicity associated with this DNA adduct.