Base-Sequence Dependence of Covalent Binding of Benzo[a]pyrene Diol Epoxide to Guanine in Oligodeoxyribonucleotides

The base-sequence dependence of the yield of the covalent binding reaction of (+)-anti-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] with the exocyclic amino group of guanine surrounded by different flanking bases X and Y in the single-stranded oligonucleotide d(CTATXGYTATC) was investigated. With an initial ratio of [(+)-anti-BPDE]/[oligonucleotide strand] = 2, the percentage of modified strands varied from 20 ± 2% when the modified dG was surrounded by pyrimidines to 5–7% when the central dG was surrounded by purines. The trans/cis ratio of (+)-anti-BPDE-N²-dG adducts was in the range of 3–5. The lower reaction yields observed when the modified guanine residues in single-stranded oligonucleotides are surrounded by purines rather than by pyrimidines is tentatively attributed (1) to steric effects arising from the presence of the bulkier purines flanking the reacting dG moieties on the 5′- and 3′-sides and/or (2) to noncovalent interactions between anti-BPDE and neighboring purines which decrease the probability of optimal alignment for covalent binding between the interacting moieties in the bimolecular transition-state complex. noncovalent intercalation of (+)-anti-BPDE prior to the covalent binding reaction is not a relevant process in the case of single-stranded oligonucleotides and is therefore not a critical requirement for obtaining high yields of covalent trans- and cis-(+)-anti-BPDE-N²-dG adducts in these oligonucleotide sequences.