Linked Life Data

15828825

Source:http://linkedlifedata.com/resource/pubmed/id/15828825

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2005-4-14
pubmed:abstractText
A series of adenosine 5'-phosphonate analogues were designed to mimic naturally occurring adenosine monophosphate. These compounds (1-5) were synthesized and evaluated in a cellular hepatitis C virus (HCV) replication assay. To improve cellular permeability and enhance the anti-HCV activity of these phosphonates, a bis(S-acyl-2-thioethyl) prodrug for compound 5 was prepared, and its cellular activity was determined. To elucidate the mechanism of action of these novel adenosine phosphonates, their diphosphate derivatives (1a-5a) were synthesized. Further nucleotide incorporation assays by HCV NS5B RNA-dependent RNA polymerase revealed that 2a and 3a can serve as chain terminators, whereas compounds 1a, 4a, and 5a are competitive inhibitors with ATP. Additional steady-state kinetic analysis determined the incorporation efficiency of 2a and 3a as well as the inhibition constants for 1a, 4a, and 5a. The structure-activity relationships among these compounds were analyzed, and the implication for nucleoside phosphonate drug design was discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2867-75
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Design, synthesis, and antiviral activity of adenosine 5'-phosphonate analogues as chain terminators against hepatitis C virus.
pubmed:affiliation
Drug Discovery, R&D, Valeant Pharmaceuticals International, 3300 Hyland Avenue, Costa Mesa, California 92626, USA.
pubmed:publicationType
Journal Article