Linked Life Data

16884295

Source:http://linkedlifedata.com/resource/pubmed/id/16884295

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2006-8-3
pubmed:abstractText
The polymerase activity of HIV-1 reverse transcriptase (RT) is entirely dependent on the heterodimeric structure of the enzyme. Accordingly, RT dimerization represents a target for the development of a new therapeutic class of HIV inhibitors. We previously demonstrated that the N-3-ethyl derivative of 2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5' '-(4' '-amino-1' ',2' '-oxathiole-2' ',2' '-dioxide)thymine (TSAO-T) destabilizes the inter-subunit interactions of HIV-1 RT [Sluis-Cremer, N.; Dmietrinko, G. I.; Balzarini, J.; Camarasa, M.-J.; Parniak, M. A. Biochemistry 2000, 39, 1427-1433]. In the current study, we evaluated the ability of 64 TSAO-T derivatives to inhibit RT dimerization using a novel screening assay. Five derivatives were identified with improved activity compared to TSAO-T. Four of these harbored hydrophilic or aromatic substituents at the N3 position. Furthermore, a good correlation between the ability of the TSAO-T derivatives to inhibit RT dimerization and the enzyme's polymerase activity was also observed. This study provides an important framework for the rational design of more potent inhibitors of RT dimerization.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4834-41
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Structure-activity relationships of [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]- 3'-spiro-5' '-(4' '-amino-1' ',2' '-oxathiole-2' ',2' '-dioxide)thymine derivatives as inhibitors of HIV-1 reverse transcriptase dimerization.
pubmed:affiliation
Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. cremern@dom.pitt.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural