NUCLEAR-MAGNETIC-RESONANCE SOLUTION STRUCTURE OF AN UNDECANUCLEOTIDE DUPLEX WITH A COMPLEMENTARY THYMIDINE BASE OPPOSITE A 10R ADDUCT DERIVED FROM TRANS ADDITION OF A DEOXYADENOSINE N-6-AMINO GROUP TO (-)-(7R,8S,9R,10S)-7,8-DIHYDROXY-9,10-EPOXY-7,8,9,10-TETRAHYDROBENZO[A]PYRENE

The solution structure of a modified undecamer duplex containing (-)-(7R,8S,9R,10S)-7,8-dihydroxy-9,10,-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene covalently bonded through trans ring opening at C10 of the epoxide by the N-6-amino group of deoxyadenosine (dA) was studied. This diol epoxide 1 diastereomer has the benzylic 7-hydroxyl group and the epoxide oxygen cis. The modified nucleotide residue has R chirality at C10 of the hydrocarbon (10R adduct). The undecamer duplex d(C(1)G(2)G(3)T(4)C(5)A*(6)C(7)G(8)A(9)G(10)G(11)). d(C(12)C(13)T(14)C(15)G(16)T(17)G(18)A(19)C(20)C(21)G(22)) has a complementary T opposite the modified dA (dA*6 is the modified dA). Exchangeable and nonexchangeable proton assignments were made using 2D TOCSY, NOESY, and water/NOESY NMR spectroscopy. The hybrid complete relaxation matrix program MORASS was used to generate NOESY distance constraints for iterative refinement using distance-restrained molecular dynamics calculations. The refined structure showed the hydrocarbon intercalated from the major groove between dA*6-T17 and dC5-dG18 base pairs. The modified dA*6 was in the normal anti configuration and showed Watson-Crick base pairing to T17 opposite. The chemical shifts of the hydrocarbon protons and the unusual shifts of sugar protons were accounted for by the intercalated orientation of the hydrocarbon.