Linked Life Data

11527047

Source:http://linkedlifedata.com/resource/pubmed/id/11527047

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-8-30
pubmed:abstractText
The beta-L-nucleoside analogue beta-L-2',3'-dideoxy adenosine (beta-L-ddA) has been shown to exhibit limited antiviral activities. This was attributed to its rapid catabolism through cleavage of the glycosidic bond and poor phosphorylation to the nucleotide beta-L-2',3'-dideoxyadenosine-5'-mono phosphate (beta-L-ddAMP) (Placidi et al., 2000). However, the nucleotide beta-L-2',3'-dideoxyadenosine-5'-triphosphate (beta-L-ddATP) inhibited the activity of both HIV-1 reverse transcriptase (RT) and viral DNA polymerase isolated from woodchuck hepatitis virus-infected serum (a model of hepatitis B) with an inhibitory concentration (IC50) of 2.0 microM without inhibiting human DNA polymerases alpha, beta, or gamma up to a concentration of 100 microM. These results suggested that prodrugs of beta-L-ddAMP may bypass the poor metabolic activation of beta-L-ddA and lead to more potent and selective antiviral activity. Therefore, the mononucleoside phosphotriester derivative of beta-L-ddAMP incorporating the S-pivaloyl-2-thioethyl (tButylSATE) groups, beta-L-ddAMP-bis(tButylSATE) was synthesized. Beta-L-ddAMP-bis(tButylSATE) inhibited HIV replication in human peripheral blood mononuclear cells (PBMCs) and HBV replication in 2.2.15 cells with effective concentrations (EC50s) of 2 and 80 nM, respectively. Intracellular metabolism of beta-L-ddAMP-bis(tButylSATE) demonstrated that beta-L-ddATP was the predominant intracellular metabolite in PBMC and liver cells. The intracellular half-life of beta-L-ddATP was 5.4 and 9.2 h in HepG2 and PBMCs, respectively. The intracellular concentrations of beta-L-ddATP were maintained above the EC50 for the inhibition of HIV RT and hepatitis B virus (HBV) for as long as 24 h after removal of the drug.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0956-3202
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
99-108
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11527047-Animals, pubmed-meshheading:11527047-Anti-HIV Agents, pubmed-meshheading:11527047-Antiviral Agents, pubmed-meshheading:11527047-Chromatography, High Pressure Liquid, pubmed-meshheading:11527047-DNA-Directed DNA Polymerase, pubmed-meshheading:11527047-Dideoxyadenosine, pubmed-meshheading:11527047-Dideoxynucleotides, pubmed-meshheading:11527047-HIV, pubmed-meshheading:11527047-Half-Life, pubmed-meshheading:11527047-Hematopoietic Stem Cells, pubmed-meshheading:11527047-Hepatitis B virus, pubmed-meshheading:11527047-Hepatocytes, pubmed-meshheading:11527047-Humans, pubmed-meshheading:11527047-Inhibitory Concentration 50, pubmed-meshheading:11527047-Lamivudine, pubmed-meshheading:11527047-Leukocytes, Mononuclear, pubmed-meshheading:11527047-Marmota, pubmed-meshheading:11527047-RNA-Directed DNA Polymerase, pubmed-meshheading:11527047-Reverse Transcriptase Inhibitors, pubmed-meshheading:11527047-Tumor Cells, Cultured, pubmed-meshheading:11527047-Virus Replication
pubmed:year
2001
pubmed:articleTitle
Antiviral activity and intracellular metabolism of bis(tButylSATE) phosphotriester of beta-L-2',3'dideoxyadenosine, a potent inhibitor of HIV and HBV replication.
pubmed:affiliation
Department of Pharmacology, University of Alabama at Birmingham, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't