https://scholars.lib.ntu.edu.tw/handle/123456789/638323
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Chang, C N | en_US |
dc.contributor.author | SHIN-LIAN DOONG | en_US |
dc.contributor.author | Zhou, J H | en_US |
dc.contributor.author | Beach, J W | en_US |
dc.contributor.author | Jeong, L S | en_US |
dc.contributor.author | Chu, C K | en_US |
dc.contributor.author | Tsai, C H | en_US |
dc.contributor.author | Cheng, Y C | en_US |
dc.contributor.author | Liotta, D | en_US |
dc.contributor.author | Schinazi, R | en_US |
dc.date.accessioned | 2024-01-10T02:00:25Z | - |
dc.date.available | 2024-01-10T02:00:25Z | - |
dc.date.issued | 1992-07-15 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/638323 | - |
dc.description.abstract | 2',3'-Dideoxy-3'-thiacytidine (+/-)-SddC) was found to have potent activity against human hepatitis B virus as well as human immunodeficiency viruses in culture. The (-)form ((-)-SddC) which is resistant to deoxycytidine deaminase was found to be the more active antiviral stereoisomer than the (+)-form ((+)-SddC). The (+)-SddC is susceptible to deamination by deoxycytidine deaminase and is 25- and 12-fold more toxic than (-)-SddC in CEM cells in terms of anti-cell growth and anti-mitochondrial DNA synthesis, respectively. Similar results were obtained using a mixture of their 5-fluoro analogs ((+/-)-FSddC). Unlike 2',3'-dideoxycytidine, which is a potent inhibitor of mitochondrial DNA synthesis and results in such delayed toxicity as peripheral neuropathy with long term usage, (-)-SddC does not affect mitochondrial DNA synthesis. The (-)form is phosphorylated to (-)-SddCMP and is subsequently converted to (-)-SddCDP and (-)-SddCTP. One additional major metabolite which has been tentatively assigned the name "(-)-SddCMP sialate" was also identified. No significant difference in terms of the profiles of the metabolites was found between 4 and 24 h. There is an appreciable amount of (-)-SddCTP detectable 24 h after removal of the drug. (-)-SddCTP was also found to be approximately 3-fold more potent than (+)-SddCTP in inhibiting human hepatitis B virus DNA polymerase. This is the first nucleoside analog with the unnatural sugar configuration demonstrated to have antiviral activity. | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | The Journal of biological chemistry | en_US |
dc.title | Deoxycytidine deaminase-resistant stereoisomer is the active form of (+/-)-2',3'-dideoxy-3'-thiacytidine in the inhibition of hepatitis B virus replication | en_US |
dc.type | journal article | en |
dc.identifier.pmid | 1321132 | - |
dc.identifier.scopus | 2-s2.0-0026697262 | - |
dc.identifier.url | https://api.elsevier.com/content/abstract/scopus_id/0026697262 | - |
dc.relation.journalvolume | 267 | en_US |
dc.relation.journalissue | 20 | en_US |
dc.relation.pageend | 13942 | en_US |
item.openairetype | journal article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.fulltext | no fulltext | - |
item.grantfulltext | none | - |
item.languageiso639-1 | en | - |
item.cerifentitytype | Publications | - |
crisitem.author.dept | Microbiology | - |
crisitem.author.orcid | 0000-0002-0936-3858 | - |
crisitem.author.parentorg | College of Medicine | - |
顯示於: | 微生物學科所 |
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