These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Synthesis of oligodeoxynucleotides containing a single 6alpha- or 6beta-diastereoisomer of N2-(estradiol-6-yl)-2'-deoxyguanosine.
    Author: Itoh S, Shibutani S, Ikegami M, Watanabe S, Laxmi YR, Suzuki N, Kohda K, Takanashi K, Yoshizawa I.
    Journal: Chem Res Toxicol; 2006 Mar; 19(3):450-6. PubMed ID: 16544951.
    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 dG and dA adducts in DNA. N(2)-[Estradiol-6(alpha or beta)-yl]-2'-deoxyguanosine [dG-N(2)-6(alpha or beta)-E(2)] lacking a 2-OH moiety may also be formed through sulfonation of 6-hydroxyestrogen. To explore the biological properties of such estrogen-DNA adducts, oligodeoxynucleotides modified by estrogen-derived DNA adduct were prepared by chemical synthesis. Initially, 6alpha- and 6beta-aminoestradiol 17-acetate (6alpha- and 6beta-NH(2)-E(2) 17Ac) were prepared by reductive amination of 6-oxo-estradiol 3,17-diacetate. The DMT-phosphoramidite derivative of N(2)-(3,17-diacetoxyestradiol-6alpha-yl)-2'-deoxyguanosine and its 6beta-isomer were prepared by coupling 5'-O-(4,4'-dimethoxytrityl)-2-fluoro-O(6)-[2-(4-nitrophenyl)ethyl]-2'-deoxyinosine separately with 6alpha- and 6beta-forms of NH(2)-E(2) 17Ac, respectively, followed by selective acetylation of the steroidal 3-hydroxyl group. The desired oligodeoxynucleotide containing a single dG-N(2)-6alpha-E(2) or dG-N(2)-6beta-E(2) was prepared efficiently by an automated DNA synthesizer. Synthesis of these site-specifically modified oligodeoxynucleotides will benefit further research into the biological properties and three-dimensional structure of 6alpha- and 6beta-diastereoisomers of estrogen-DNA adducts.
    [Abstract] [Full Text] [Related] [New Search]