C. De Los Santos et al., NMR characterization of a DNA duplex containing the major acrolein-deriveddeoxyguanosine adduct gamma-OH-1,N-2-propano-2 '-deoxyguanosine, J BIOL CHEM, 276(12), 2001, pp. 9077-9082
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.