Linked Life Data

18800766

Source:http://linkedlifedata.com/resource/pubmed/id/18800766

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2008-9-19
pubmed:abstractText
GC dinucleosides exhibiting a phosphoramidate internucleosidic linkage with neutral, amphiphile, positively or negatively charged side chains were synthesized. Their potential inhibitory effect on the hepatitis C virus (HCV) NS5B polymerase was evaluated in vitro and in HCV replicon containing cells. Whereas the amphiphile and the positively charged analogues were found to be inactive, the neutral (1) and the negatively charged (4) ones inhibited enzyme activity when tested as a diastereoisomeric mixture. The most potent inhibitor proved to be the Sp isomer of the 5'-thiophosphorylated dinucleotide bearing the carboxylic side chain (8) (IC 50 of 25 microM in vitro and an EC 50 of 9 microM in HCV subgenomic replicon). Molecular modeling suggests that the phosphoramidate dinucleoside (8) is stabilized in the active site by interactions with magnesium ions and lysine and arginine residues of the polymerase.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
25
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5745-57
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Phosphoramidate dinucleosides as hepatitis C virus polymerase inhibitors.
pubmed:affiliation
Institut des Biomolécules Max Mousseron, UMR 5247 CNRS - Universite Montpellier 1 - Universite Montpellier 2, Place Eugene Bataillon, CC1704, 34095 Montpellier Cedex 5, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't