NMR Characterization of a DNA Duplex Containing the Major Acrolein-derived Deoxyguanosine Adduct gamma -OH-1,-N2-Propano-2'-deoxyguanosine (original) (raw)

2001, Journal of Biological Chemistry

The environmental and endogenous mutagen acrolein reacts with cellular DNA to produce several isomeric 1,N 2propanodeoxyguanosine adducts. High resolution NMR spectroscopy was used to establish the structural features of the major acrolein-derived adduct, ␥-OH-1,N 2 -propano-2-deoxyguanosine. In aqueous solution, this adduct was shown to assume a ring-closed form. In contrast, when ␥-OH-1,N 2 -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 ␥-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.