O6-alkyl-2'-deoxyguanosines are alkylation products of guanine by nitrosamines, that during replication lead to G to A transition mutations. A structure of the O6-benzylguanine adduct O6-BnG with the Dpo4 polymerase, paired opposite cytosine, exhibited a wobble base pair, and thermal analysis suggested destabilization relative to the G:C base pair. However, incorporation of the perimidinone-derived synthetic nucleoside (dPer) opposite O6-BnG stabilizes the duplex. This study presents the structure of a duplex containing the O6-BnG:dPer base pair. The O6-BnG does not form Watson-Crick hydrogen bonds with dPer, but instead exhibits stacking interactions within the duplex. The presentation will discuss the implications for how alkylation and hydrophobic synthetic probes influence base pairing interactions in DNA. Supported by the Vanderbilt University Center in Molecular Toxicology, P30 ES-00267 and European Research Council (260341). Crystallographic data were collected on the 21-ID-D beamline of the Life Sciences Collaborative Access Team (LS-CAT) at the APS (Argonne National Laboratory, Argonne, IL).

Stabilization of a O<sup>6</sup>-benzyl-2'-deoxyguanosine adduct by a perimidinone-derived synthetic nucleoside via unique stacking interactions

244th National Meeting (2012)

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Stabilization of a O6-benzyl-2'-deoxyguanosine adduct by a perimidinone-derived synthetic nucleoside via unique stacking interactions

Stabilization of a O⁶-benzyl-2'-deoxyguanosine adduct by a perimidinone-derived synthetic nucleoside via unique stacking interactions