CHEMICAL CHARACTERIZATION OF DNA ADDUCTS DERIVED FROM THE CONFIGURATIONALLY ISOMERIC BENZO[C]PHENANTHRENE-3,4-DIOL 1,2-EPOXIDES
CHEMICAL CHARACTERIZATION OF DNA ADDUCTS DERIVED FROM THE CONFIGURATIONALLY ISOMERIC BENZO[C]PHENANTHRENE-3,4-DIOL 1,2-EPOXIDES
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DOI：
10.1021/ja00242a040
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发表时间：
1987-04-15
影响因子：
15
通讯作者：
JERINA, DM
中科院分区：
文献类型：
--
作者：
AGARWAL, SK;SAYER, JM;JERINA, DM
The chemical structures of 16 principal adducts formed from the deoxyadenosine and deoxyguanosine residues of DNA upon reaction in vitro with the four configurationally isomeric 3,4-diol 1,2-epoxides derived from benzo[c]phenanthrene-trans-3,4-dihydrodiol have been elucidated. These adducts (one cis and one trans addition product derived from each of the four configurationally isomeric diol epoxides and either deoxyguanosine or deoxyadenosine) were prepared in quantities sufficient for structural studies via the reactions of the diol epoxides with deoxyguanylic and deoxyadenylic acids, followed by enzymatic removal of the phosphate group. The site of covalent attachment of the diol epoxide moiety to the nucleoside residue in these adducts is at the exocyclic amino group. For most of the deoxyguanosine adducts, the linkage between this nitrogen and C1 of the tetrahydrobenzo[c]phenanthrene system was established directly by NMR decoupling experiments using the pentaacetate esters of the adducts. Since the lack of observable NMR signals for the exocyclic N-H of adenine in the pentaacetates of the deoxyadenosine adducts made such decoupling experiments impossible, the site of attack of deoxyadenosine was deduced to be at the exocyclic N6 by a combination of chemical stability considerations and pH titration (pK=3.8 for a representative unacetylated adduct). The stereochemistry (cis or trans opening of the epoxide) of each adduct was assigned on the basis of the 1H NMR spectrum of the corresponding pentaacetate ester. An empirical correlation has been found between R-absolute configuration at the benzylic carbon of the tetrahydroaromatic moiety and negative ellipticity of the major CD band for these benzo[c]phenanthrene diol epoxide adducts of deoxyguanosine and deoxyadenosine, as well as for analogous adducts derived from purine nucleosides and benzo[a]pyrene-7,8-diol 9,10-epoxides.
