| pubmed-article:11040039 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11040039 | lifeskim:mentions | umls-concept:C0178719 | lld:lifeskim |
| pubmed-article:11040039 | lifeskim:mentions | umls-concept:C0011209 | lld:lifeskim |
| pubmed-article:11040039 | lifeskim:mentions | umls-concept:C0676775 | lld:lifeskim |
| pubmed-article:11040039 | lifeskim:mentions | umls-concept:C0961772 | lld:lifeskim |
| pubmed-article:11040039 | pubmed:issue | 5 | lld:pubmed |
| pubmed-article:11040039 | pubmed:dateCreated | 2000-10-30 | lld:pubmed |
| pubmed-article:11040039 | pubmed:abstractText | Cyclosaligenyl-2',3'-didehydro-2', 3'-dideoxythymidine-5'-monophosphate (cycloSal-d4TMP) is a potent and selective inhibitor of human immunodeficiency virus replication in cell culture and differs from other nucleotide prodrug approaches in that it is designed to selectively deliver the nucleotide 5'-monophosphate by a controlled, chemically induced hydrolysis. Its antiviral efficacy in cell culture is at least as good as, if not superior to, that of d4T. CycloSal-d4TMP was found to lead to the efficient intracellular release of d4TMP in a variety of cell lines, including both wild-type CEM and thymidine kinase-deficient CEM/TK(-) cells. Under similar experimental conditions, exposure of CEM/TK(-) cells to d4T failed to result in significant d4TTP levels. The intracellular conversion of cycloSal-d4TMP proved to be both time and dose dependent. The half-life of d4TTP generated intracellularly from d4T- or cycloSal-d4TMP-treated CEM cells was approximately 3.5 h, and the intracellular ratios of d4TTP/d4TMP in cells exposed to cycloSal-d4TMP gradually increased from 1 to 3.4 upon prolonged incubation. Radiolabeled cycloSal-d4TMP could be separated as its two R(p) and S(p) diastereomers on high-performance liquid chromatography. The R(p) diastereomer of cycloSal-d4TMP was 3- to 7-fold more efficient in releasing d4TMP and generating d4TTP than the S(p) cycloSal-d4TMP diastereomer. This correlated well with the 5-fold more pronounced antiviral activity of the R(p) diastereomer versus the S(p) diastereomer. d4TMP is a poor substrate for the cytosolic 5'(3')-deoxyribonucleotidase (V(max)/K(m) for d4TMP: 0.08 of V(max)/K(m) for dTMP) and is only slowly hydrolyzed to d4T. This contributes to the efficient conversion of the prodrug of d4TTP. | lld:pubmed |
| pubmed-article:11040039 | pubmed:language | eng | lld:pubmed |
| pubmed-article:11040039 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11040039 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:11040039 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11040039 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11040039 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11040039 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11040039 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11040039 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11040039 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11040039 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11040039 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11040039 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11040039 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11040039 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11040039 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11040039 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11040039 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11040039 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:11040039 | pubmed:issn | 0026-895X | lld:pubmed |
| pubmed-article:11040039 | pubmed:author | pubmed-author:De ClercqEE | lld:pubmed |
| pubmed-article:11040039 | pubmed:author | pubmed-author:MeierCC | lld:pubmed |
| pubmed-article:11040039 | pubmed:author | pubmed-author:BianchiVV | lld:pubmed |
| pubmed-article:11040039 | pubmed:author | pubmed-author:BalzariniJJ | lld:pubmed |
| pubmed-article:11040039 | pubmed:author | pubmed-author:PernoC FCF | lld:pubmed |
| pubmed-article:11040039 | pubmed:author | pubmed-author:RampazzoCC | lld:pubmed |
| pubmed-article:11040039 | pubmed:author | pubmed-author:AquaroSS | lld:pubmed |
| pubmed-article:11040039 | pubmed:author | pubmed-author:KnispelTT | lld:pubmed |
| pubmed-article:11040039 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:11040039 | pubmed:volume | 58 | lld:pubmed |
| pubmed-article:11040039 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:11040039 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:11040039 | pubmed:pagination | 928-35 | lld:pubmed |
| pubmed-article:11040039 | pubmed:dateRevised | 2007-11-15 | lld:pubmed |
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| pubmed-article:11040039 | pubmed:year | 2000 | lld:pubmed |
| pubmed-article:11040039 | pubmed:articleTitle | Cyclosaligenyl-2',3'-didehydro-2',3'-dideoxythymidine monophosphate: efficient intracellular delivery of d4TMP. | lld:pubmed |
| pubmed-article:11040039 | pubmed:affiliation | Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium. jan.balzarini@rega.kuleuven.ac.be | lld:pubmed |
| pubmed-article:11040039 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:11040039 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:11040039 | lld:pubmed |
