Effect of absolute configuration on the optical and NMR properties of oligonucleotides containing benzo[a]pyrene abducts at N-6 of deoxyadenosine

For oligonucleotide duplexes derived from trans opening of benzo[a]pyrene d iol epoxides (BaP DEs) by the exocyclic N-6-amino group of deoxyadenosine ( dA), the hydrocarbon is intercalated toward the 5'-end of the modified stra nd when the configuration at the site of attachment of the base to the hydr ocarbon (C-10) is R, and toward the 3'-end when this configuration is S. In oligonucleotide 11-mer duplexes modified by BaP DE-1 (benzylic 7-OH and ep oxide oxygen cis) and DE-2 (7-OH and epoxide oxygen trans), as well as 7,8, 9,10-tetrahydro BaP 9,10-epoxide, 10R adducts had consistently higher (5-9 degrees C) T-m values than the corresponding 10S adducts. Dodecamer duplexe s from the HPRT gene with trans opened 10S (but not those with 10R) BaP DE- 2 adducts at either of two adjacent dA residues exhibited blue shifts at si milar to 350 nm at temperatures well below the T-m. We propose that these b lue shifts result from a conformation in which the hydrocarbon is not stack ed with the DNA bases.