Linked Life Data

8913335

Source:http://linkedlifedata.com/resource/pubmed/id/8913335

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1996-12-26
pubmed:abstractText
We compared the inhibition of HIV-1 reverse transcriptase (RT) by 1-[2',5'-bis-O-(t-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'- spiro-5"-(4"-amino-1", 2"-oxathiole-2",2"-dioxide)-3-ethylthymine (TSAOe3T) and the nonnucleoside RT inhibitor (NNRTI) 9-aminonevirapine (9-NH2N). Both compounds were equally effective against p51/p66 heterodimeric RT RNA-dependent DNA polymerase activity, although TSAOe3T was a much better inhibitor of the p51/p51 and p66/p66 RT homodimers. Inhibition by TSAOe3T and 9-NH2N combinations was essentially additive. TSAOe3T did not protect either free RT or the RT-template/ primer-deoxynucleoside triphosphate ternary complex from irreversible inactivation by the photolabel 9-azidonevirapine. Slight protection of the RT-template/primer binary complex was noted, but only at high TSAOe3T/photolabel ratios. Analysis of RT polymerization product profiles under both continuous- and single-processive cycle conditions showed that 9-NH2N prevented the formation of full-length product with a corresponding accumulation of smaller polymerization products. In contrast, all products formed in the absence of inhibitor, including full-length product, were noted in TSAOe3T-inhibited reactions, albeit at reduced levels. TSAOe3T thus inhibits HIV-1 RT by a different mechanism than NNRTI such as nevirapine. Our data suggest that TSAOe3T and 9-NH2N interact differently with HIV-1 RT, perhaps by binding to distinct sites on the enzyme.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1057-64
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Differences in the inhibition of human immunodeficiency virus type 1 reverse transcriptase DNA polymerase activity by analogs of nevirapine and [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1", 2"-oxathiole-2",2"-dioxide] (TSAO).
pubmed:affiliation
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't