Linked Life Data

12482230

Source:http://linkedlifedata.com/resource/pubmed/id/12482230

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2002-12-16
pubmed:abstractText
A new and efficient method is described for the synthesis in gram quantities of the benzo[a]pyrene (B[a]P) metabolic adducts of 2'-deoxyguanosine (dG) and 2'-deoxyadenosine (dA) substituted, respectively, at the N(2)- and N(6)- positions. When the racemic form of the tris(benzoyloxy)amine 5 (related to the notoriously carcinogenic epoxydiol 2) is coupled with the bromoinosine derivative 6 by means of a Buchwald-Hartwig reaction, the expected pair of diastereomers, 7 and 8, is obtained in high (combined) yield. Selective deblocking of this mixture then gave cleanly the pair of diastereomers 9. These were used in the synthesis of a series of DNA oligomers via their 5'-O-DMT-3'-O-phosphoramidites (10) using standard automated methods. Coupling efficiencies were 94-98% at the point of introduction of the xeno-2'-deoxynucleoside, and in all cases the mixtures of the two diastereomeric oligomers (DMT-off stage) were easily separated by HPLC. By a similar sequence of reactions beginning with 5 and the protected 6-bromopurine 2'-deoxynucleoside 11, it was possible with equal efficiency to introduce the N(6)-modified diastereomers (16) of dA into oligomeric DNA. Circular dichroism measurements were used to establish the fundamental configurations at the xeno-2'-deoxynucleoside site for each of the oligomers. Mass spectral data in both the dG and the dA series confirmed the presence of the xeno-2'-deoxynucleoside in the oligomers. This was complemented by enzymatic degradation of one of the oligomers from each of the series. In both of these cases, after HPLC separation, circular dichroism measurements on the reisolated xenonucleoside also confirmed its presence in the oligomer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0893-228X
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1489-94
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Efficient synthesis of the benzo[a]pyrene metabolic adducts of 2'-deoxyguanosine and 2'-deoxyadenosine and their direct incorporation into DNA.
pubmed:affiliation
Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, USA. francis@pharm.sunysb.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.