Covalent binding of benzo[a]pyrenediol epoxides to polynucleotides

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Abstract
Spectroscopic studies on the trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene- (anti-BPDE-) modified synthetic polynucleotide solutions reveal interesting sequence-dependent stereoselective covalent binding of anti-BPDE to DNA. Absorption spectral results indicate that the G .cntdot. C polymers are much more reactive than the A .cntdot. T polymers toward this metabolite and the homopolymer suffers higher modification than its corresponding alternating polynucleotide. The covalently attached anti-BPDE exhibits only a 2-3 nm red shift in the guanine-containing polynucleotide and native DNA solutions as opposed to the 8-nm red shift in poly(G) and none in the A .cntdot. T polymers. Distinct stereoselectivities are exhibited by poly(dG-dC) .cntdot. poly(dG-dC) vs. poly(dG) .cntdot. poly(dC) as suggested by the oppositely signed CD in the pyrene spectral region. Comparison with the syn-BPDE modified polynucleotides reveals some interesting differences with its anti diastereomer. Significant contributions from the intercalated syn-BPDE are apparent in the modified guanine-containing polynucleotides as indicated by the appearance of 10-nm red-shifted shoulders. In contrast to the strong dependence on polynucleotides for anti-BPDE, the rate of hydrolysis of syn-BPDE appears to be insensitive to their presence in the solution. Anti-BPDE modification on the 50 .mu.M hexaamminecobalt-induced Z-form poly(dG-dC) .cntdot. poly(dG-dC) is much less extensive than its corresponding B form, possibly the consequence of both structural and ionic strength factors. The spectral characteristics of anti-BPDE bonded to these two forms are distinctly different, with the Z form resembling more closely those of A .cntdot. T polymers. Salt titration of the anti-BPDE-modified B-form poly(dG-dC) .cntdot. poly(dG-dC) suggests that the "externally" bound moiety becomes intercalated under high-salt conditions as judged by the CD spectral red shift and concomitant intensity enhancement.

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