| Abstract
| - DNA damage induced by estrogens is associated with developing breast, ovary, and endometrial cancers.The quinone of 2-hydroxyestrogen (2-OHE), a major estrogen metabolite, produces 2-OHE-derived dGand dA adducts in DNA. N2-[Estradiol-6(α or β)-yl]-2‘-deoxyguanosine [dG-N2-6(α or β)-E2] lacking a2-OH moiety may also be formed through sulfonation of 6-hydroxyestrogen. To explore the biologicalproperties of such estrogen−DNA adducts, oligodeoxynucleotides modified by estrogen-derived DNAadduct were prepared by chemical synthesis. Initially, 6α- and 6β-aminoestradiol 17-acetate (6α- and6β-NH2-E2 17Ac) were prepared by reductive amination of 6-oxo-estradiol 3,17-diacetate. The DMT-phosphoramidite derivative of N2-(3,17-diacetoxyestradiol-6α-yl)-2‘-deoxyguanosine and its 6β-isomerwere prepared by coupling 5‘-O-(4,4‘-dimethoxytrityl)-2-fluoro-O6-[2-(4-nitrophenyl)ethyl]-2‘-deoxyinosineseparately with 6α- and 6β-forms of NH2-E2 17Ac, respectively, followed by selective acetylation of thesteroidal 3-hydroxyl group. The desired oligodeoxynucleotide containing a single dG-N2-6α-E2 or dG-N2-6β-E2 was prepared efficiently by an automated DNA synthesizer. Synthesis of these site-specificallymodified oligodeoxynucleotides will benefit further research into the biological properties and three-dimensional structure of 6α- and 6β-diastereoisomers of estrogen−DNA adducts.
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