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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
22
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pubmed:dateCreated |
1992-12-1
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pubmed:abstractText |
We have demonstrated that herpes simplex 1 (HSV1) thymidine kinase (TK) shows no stereospecificity for D- and L-beta-nucleosides. In vitro, L enantiomers are not recognized by human TK, but function as specific substrates for the viral enzyme in the order: L-thymidine (L-T) >> 2'-deoxy-L-guanosine (L-dG) > 2'-deoxy-L-uridine (L-dU) > 2'-deoxy-L-cytidine (L-dC) > 2'-deoxy- L-adenosine (L-dA). HSV1 TK phosphorylates both thymidine enantiomers to their corresponding monophosphates with identical efficiency and the Ki of L-T (2 microM) is almost identical to the Km for the natural substrate D-T (2.8 microM). The L enantiomer reduces the incorporation of exogenous [3H]T into cellular DNA in HeLa TK-/HSV1 TK+ but not in wild-type HeLa cells, without affecting RNA, protein synthesis, cell growth, and viability. L-T markedly reduces HSV1 multiplication in HeLa cells. Our observations could lead to the development of a novel class of antiviral drugs characterized by low toxicity.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyribonucleosides,
http://linkedlifedata.com/resource/pubmed/chemical/Leucine,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Uridine
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
35
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pubmed:owner |
NLM
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pubmed:authorsComplete |
N
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pubmed:pagination |
4214-20
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:1331461-Cell Division,
pubmed-meshheading:1331461-Cell Survival,
pubmed-meshheading:1331461-Deoxyribonucleosides,
pubmed-meshheading:1331461-HeLa Cells,
pubmed-meshheading:1331461-Humans,
pubmed-meshheading:1331461-Leucine,
pubmed-meshheading:1331461-Simplexvirus,
pubmed-meshheading:1331461-Stereoisomerism,
pubmed-meshheading:1331461-Thymidine,
pubmed-meshheading:1331461-Thymidine Kinase,
pubmed-meshheading:1331461-Uridine
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pubmed:year |
1992
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pubmed:articleTitle |
L-thymidine is phosphorylated by herpes simplex virus type 1 thymidine kinase and inhibits viral growth.
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pubmed:affiliation |
Istituto di Genetica Biochimica ed Evoluzionistica, CNR, Pavia, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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