Linked Life Data

16544951

Source:http://linkedlifedata.com/resource/pubmed/id/16544951

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-3-20
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0893-228X
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
450-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Synthesis of oligodeoxynucleotides containing a single 6alpha- or 6beta-diastereoisomer of N2-(estradiol-6-yl)-2'-deoxyguanosine.
pubmed:affiliation
Hokkaido Pharmaceutical University School of Pharmacy, 7-1, Katsuraoka-cho, Otaru, Hokkaido 047-0264, Japan. itoh-m33@hokuyakudai.ac.jp
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural