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Solution structures of the (-)-cis-anti-benzo[a]pyrenyl-N{sup 2}-dG adduct and stereoisomerically related DNA adduct duplexes

Conference ·
OSTI ID:538957
;  [1];  [2]
  1. Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
  2. Oak Ridge National Lab., TN (United States); and others

A combined NMR/computational study of the (-)-cis-anti-[BP]dG*.dC duplex completes our analysis of the structures of all four isomeric adducts derived from the addition of (+)- and (-)-anti-benzo[a]pyrene diol epoxides (BPDE) to N2-dG in the same 11-mer DNA duplex. In the (+)- and (-)-cis-adducts, the pyrenyl residues are intercalated but the modified deoxyguanines are displaced into the minor and major grooves respectively (base-displaced intercalation model). In contrast, in the (+)- and (-)-trans-adducts, the pyrenyl residues are located in the minor groove, and are oriented toward the 5{prime} or the 3{prime} end of the modified strand, respectively. Our key finding is that chiral anti-BPDE stereoisomers give rise to N2-dG adducts with opposite 5{prime} or 3{prime} orientations of the pyrenyl residues relative to the modified dG (trans-adducts), or with opposite rotations of the pyrenyl ring system about the helix axis (cis-adducts).

OSTI ID:
538957
Report Number(s):
CONF-960807--
Country of Publication:
United States
Language:
English