Synthesis of Oligodeoxynucleotides Containing a Single 6- or 6![]()
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- 作者：Shinji Itoh ; Shinya Shibutani ; Masazumi Ikegami ; Shingo Watanabe ; Y. R. Santosh Laxmi ; Naomi Suzuki ; Kohfuku Kohda ; Kaori Takanashi ; and Itsuo Yoshizawa
- 刊名：Chemical Research in Toxicology
- 出版年：2006
- 出版时间：March 2006
- 年：2006
- 卷：19
- 期：3
- 页码：450 - 456
- 全文大小：133K
- 年卷期：v.19,no.3(March 2006)
- ISSN：1520-5010
文摘
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(
rs/alpha.gif" BORDER=0> or rs/beta2.gif" BORDER=0 ALIGN="middle">)-yl]-2'-deoxyguanosine [dG-N2-6(rs/alpha.gif" BORDER=0> or rs/beta2.gif" BORDER=0 ALIGN="middle">)-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, 6rs/alpha.gif" BORDER=0>- and 6rs/beta2.gif" BORDER=0 ALIGN="middle">-aminoestradiol 17-acetate (6rs/alpha.gif" BORDER=0>- and6rs/beta2.gif" BORDER=0 ALIGN="middle">-NH2-E2 17Ac) were prepared by reductive amination of 6-oxo-estradiol 3,17-diacetate. The DMT-phosphoramidite derivative of N2-(3,17-diacetoxyestradiol-6rs/alpha.gif" BORDER=0>-yl)-2'-deoxyguanosine and its 6rs/beta2.gif" BORDER=0 ALIGN="middle">-isomerwere prepared by coupling 5'-O-(4,4'-dimethoxytrityl)-2-fluoro-O6-[2-(4-nitrophenyl)ethyl]-2'-deoxyinosineseparately with 6rs/alpha.gif" BORDER=0>- and 6rs/beta2.gif" BORDER=0 ALIGN="middle">-forms of NH2-E2 17Ac, respectively, followed by selective acetylation of thesteroidal 3-hydroxyl group. The desired oligodeoxynucleotide containing a single dG-N2-6rs/alpha.gif" BORDER=0>-E2 or dG-N2-6rs/beta2.gif" BORDER=0 ALIGN="middle">-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 6rs/alpha.gif" BORDER=0>- and 6rs/beta2.gif" BORDER=0 ALIGN="middle">-diastereoisomers of estrogen-DNA adducts.
rs/alpha.gif" BORDER=0> or rs/beta2.gif" BORDER=0 ALIGN="middle">)-yl]-2'-deoxyguanosine [dG-N2-6(rs/alpha.gif" BORDER=0> or rs/beta2.gif" BORDER=0 ALIGN="middle">)-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, 6rs/alpha.gif" BORDER=0>- and 6rs/beta2.gif" BORDER=0 ALIGN="middle">-aminoestradiol 17-acetate (6rs/alpha.gif" BORDER=0>- and6rs/beta2.gif" BORDER=0 ALIGN="middle">-NH2-E2 17Ac) were prepared by reductive amination of 6-oxo-estradiol 3,17-diacetate. The DMT-phosphoramidite derivative of N2-(3,17-diacetoxyestradiol-6rs/alpha.gif" BORDER=0>-yl)-2'-deoxyguanosine and its 6rs/beta2.gif" BORDER=0 ALIGN="middle">-isomerwere prepared by coupling 5'-O-(4,4'-dimethoxytrityl)-2-fluoro-O6-[2-(4-nitrophenyl)ethyl]-2'-deoxyinosineseparately with 6rs/alpha.gif" BORDER=0>- and 6rs/beta2.gif" BORDER=0 ALIGN="middle">-forms of NH2-E2 17Ac, respectively, followed by selective acetylation of thesteroidal 3-hydroxyl group. The desired oligodeoxynucleotide containing a single dG-N2-6rs/alpha.gif" BORDER=0>-E2 or dG-N2-6rs/beta2.gif" BORDER=0 ALIGN="middle">-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 6rs/alpha.gif" BORDER=0>- and 6rs/beta2.gif" BORDER=0 ALIGN="middle">-diastereoisomers of estrogen-DNA adducts.