Covalent Nucleoside Adducts of Benzopyrene 7,8-Diol 9,10-Epoxides: Structural Reinvestigation and Characterization of a Novel Adenosine Adduct on the Ribose Moiety.

Article abstract of DOI:10.1021/jo00001a007

The diastereomeric 7,8-diol 9,10-epoxides metabolically derived from the carcinogenic hydrocarbon benzopyrene react with the purine bases in nucleic acids to alkylate their exocyclic amino groups.The major adducts formed from polyguanylic acid and the enantiomers of the diol epoxide-1 (the diastereomer in which the benzylic 7-hydroxyl group and the epoxide oxygen are cis) have been shown to result from cis opening of the epoxide by the N-2 amino group of guanine, rather than trans opening as had previously reported.Four adducts resulting from alkylation of the exocyclic N-6 amino group of adenosine 5'-monophosphate by racemic diol epoxide-1 have been prepared and characterized.In addition, a major adduct formed from adenosine 5'-monophosphate and (-)-(7R,8S)-diol (9R,10S)-epoxide-1, but not from its (+) enantiomer, has been identified as a product of alkylation of the 2'-hydroxyl group of the sugar.We also report a quantitative reevaluation of the extent and distribution of covalent adduct formation from calf thymus DNA and both diastereomeric benzopyrene-diol epoxides, as well as the identification of the principal DNA adducts formed from the enantiomers of diol epoxide-1.Tentative identification of several new minor adducts formed upon reaction of diol epoxide-2 with denaturated DNA is described.The present results provide additional support for our previously proposed correlation between the signs of the circular dichroism bands of these adducts and their absolute configurations at the N-substituted benzylic carbon atom.