NMR SOLUTION STRUCTURE OF A NONANUCLEOTIDE DUPLEX WITH A DG MISMATCH OPPOSITE A 10R ADDUCT DERIVED FROM TRANS ADDITION OF A DEOXYADENOSINE N-6-AMINO GROUP TO DROXY-9,10-EPOXY-7,8,9,10-TETRAHYDROBENZO[A]PYRENE

A nonanucleotide in which droxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a] pyrene (7-hydroxy group and epoxide oxygen are trans) is covalently be nded to the exocyclic N-6-amino group of deoxyadenosine through trans addition at C10 of the epoxide (10R adduct) has been synthesized. The modified oligonucleotide d(GGTCACGAG) was incorporated into the duple x d(GGTCACGAG).d(CTCGGGACC), containing a dG mismatch opposite the mo dified base (dA). Proton assignments for the solution structure of th e duplex containing the 10R adduct were made using 2D TOCSY and NOESY NMR spectra. The complete hybrid relaxation matrix program, MORASS2.0, was used to generate NOESY distance constraints for iterative refinem ent using distance-restrained molecular dynamics calculations with AMB ER4.0. The iteratively refined structure showed the hydrocarbon interc alated from the major groove immediately below the dC(4)-dG(15) base p air and oriented toward the 5'-end of the modified strand. The modifie d dA is in an anti configuration, with the dG of the GA mismatch turne d out into the major groove. Chemical shifts of the hydrocarbon proton s and unusual chemical shifts of sugar protons were accounted for by t his orientation of the adduct. The information available currently pro vides the foundation for the rational explanation of observed benzo[a] pyrene (BaP) structures and predictions for other BaP dG and dA adduct s.