Preparation and isolation of adducts in high yield derived from the binding of two benzo[a]pyrene-7,8-dihydroxy-9,10-oxide stereoisomers to the oligonucleotide d(atatgtata)

The reaction of the (+)- and (-)-enantlomers of BDPE (trans-7,8-dihydroxy-anti-9,1O-epoxy-7,8,9,10-tetrahydrobenzo-[a]pyrene) with the oligodeoxynucleotide d(ATATGTATA) in aqueous buffer solutions gives rise predominantly to trans and cis addition products at the exocydlic amino group of the single deoxyguanosine residue. The trans/cis ratios are 7:1 in the case of (+)-BPDE, and 2:1 in the case of (-)-BPDE, while the reaction yields correspond to 34 and 15% respectively, of modified strands. These relatively high reaction efficiencies, at least forthis particular type of oligonucleotide sequence, offer the possibilities of synthesizing relatively large amounts of well-defined covalent BPDE-oligonucleotide adducts (with different sequences of nucleotides flanking the modified base) for detailed spectroscopic and biochemical studies.