|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
1
|
|
pubmed:dateCreated |
2001-2-5
|
|
pubmed:abstractText |
(-)-beta-D-2,6-Diaminopurine dioxolane (DAPD), is a nucleoside reverse transcriptase (RT) inhibitor with activity against human immunodeficiency virus type 1 (HIV-1). DAPD, which was designed as a water-soluble prodrug, is deaminated by adenosine deaminase to give (-)-beta-D-dioxolane guanine (DXG). By using calf adenosine deaminase a K(m) value of 15 +/- 0.7 microM was determined for DAPD, which was similar to the K(m) value for adenosine. However, the k(cat) for DAPD was 540-fold slower than the k(cat) for adenosine. In CEM cells and peripheral blood mononuclear cells exposed to DAPD or DXG, only the 5'-triphosphate of DXG (DXG-TP) was detected. DXG-TP is a potent alternative substrate inhibitor of HIV-1 RT. Rapid transient kinetic studies show the efficiency of incorporation for DXG-TP to be lower than that measured for the natural substrate, 2'-deoxyguanosine 5'-triphosphate. DXG-TP is a weak inhibitor of human DNA polymerases alpha and beta. Against the large subunit of human DNA polymerase gamma a K(i) value of 4.3 +/- 0.4 microM was determined for DXG-TP. DXG showed little or no cytotoxicity and no mitochondrial toxicity at the concentrations tested.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120959-10508010,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120959-10606085,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120959-10858331,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120959-1283296,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120959-2495366,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120959-6731845,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120959-7520683,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120959-8496934,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120959-8622980,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120959-8891140,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120959-8937473,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120959-9671525,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120959-9890882
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2,6-diaminopurine dioxolane,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Deaminase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-HIV Agents,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Directed DNA Polymerase,
http://linkedlifedata.com/resource/pubmed/chemical/Dioxolanes,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine,
http://linkedlifedata.com/resource/pubmed/chemical/Lactic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Prodrugs,
http://linkedlifedata.com/resource/pubmed/chemical/Purine Nucleosides,
http://linkedlifedata.com/resource/pubmed/chemical/Reverse Transcriptase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/dioxolane guanosine
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jan
|
|
pubmed:issn |
0066-4804
|
|
pubmed:author |
pubmed-author:AndersonK SKS,
pubmed-author:Borroto-EsodaKK,
pubmed-author:ChiC WCW,
pubmed-author:CopelandW CWC,
pubmed-author:FengJ YJY,
pubmed-author:FurmanP APA,
pubmed-author:HillEE,
pubmed-author:JeffreyJJ,
pubmed-author:KieferL LLL,
pubmed-author:LibermanII,
pubmed-author:PainterG RGR,
pubmed-author:SchinaziR FRF,
pubmed-author:SommadossiJ PJP
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
45
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
158-65
|
|
pubmed:dateRevised |
2010-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:11120959-Adenosine Deaminase Inhibitors,
pubmed-meshheading:11120959-Anti-HIV Agents,
pubmed-meshheading:11120959-Bone Marrow Cells,
pubmed-meshheading:11120959-Cells, Cultured,
pubmed-meshheading:11120959-DNA, Viral,
pubmed-meshheading:11120959-DNA-Directed DNA Polymerase,
pubmed-meshheading:11120959-Dioxolanes,
pubmed-meshheading:11120959-Drug Resistance, Microbial,
pubmed-meshheading:11120959-Enzyme Inhibitors,
pubmed-meshheading:11120959-Guanosine,
pubmed-meshheading:11120959-HIV-1,
pubmed-meshheading:11120959-Humans,
pubmed-meshheading:11120959-Lactic Acid,
pubmed-meshheading:11120959-Microscopy, Electron,
pubmed-meshheading:11120959-Mitochondria,
pubmed-meshheading:11120959-Prodrugs,
pubmed-meshheading:11120959-Purine Nucleosides,
pubmed-meshheading:11120959-Reverse Transcriptase Inhibitors
|
|
pubmed:year |
2001
|
|
pubmed:articleTitle |
Mechanism of action of 1-beta-D-2,6-diaminopurine dioxolane, a prodrug of the human immunodeficiency virus type 1 inhibitor 1-beta-D-dioxolane guanosine.
|
|
pubmed:affiliation |
Triangle Pharmaceuticals, Durham, North Carolina 27707, USA. furmanpa@tripharm.com
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|
