Sequence specific binding of tetraols of benzo[a]pyrene-diol-epoxide to DNA in neutral and acidic solutions

Comparative binding studies of tetraols (anti- BPTs ) derived from trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetra- hydrobenzo [a]py rene (anti-BPDE) with native DNA in neutral and acidic solutions reveal that 4-5 times stronger intercalative binding occurs in the protonated duplex DNA than in the unprotonated one. Spectroscopic (absorption and circular dichroism) investigations with synthetic polynucleotides indicate that in neutral pH, anti- BPTs intercalate significantly in poly(dA-dT):poly(dA-dT), only slightly in guanine containing alternating polynucleotides poly(dG-dC): poly(dG-dC) and poly(dA-dC):poly(dG-dT), and hardly in homopolymers poly(dG):poly(dC) and poly(dA):poly(dT). In acidic solutions, on the other hand, all three alternating polynucleotides, poly(dG-dC):poly(dG-dC) in particular, exhibit strong intercalative binding to anti- BPTs although the homopolymers still lack such capability. These results are very similar to those of corresponding pyrene studies suggesting that pyrene can be a useful model compound for the DNA binding studies of benzo[a]pyrene metabolites. The observed enhanced binding of anti- BPTs in the acidic natural DNA solution is seen as the consequence of changes in base sequence preference upon base protonation.