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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1987-6-18
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pubmed:abstractText |
Adenosine dialdehyde (2'-O-[(R)-formyl(adenin-9-yl)methyl]-(R)-glyceraldehyde), formed by periodate oxidation of adenosine, is a potent inhibitor of S-adenosylhomocysteine hydrolase (EC 3.3.1.1.) in mouse L929 cells. Consequently, the dialdehyde produces an increase in intracellular levels of S-adenosylhomocysteine and subsequent inhibition of S-adenosylmethionine-dependent macromolecular methylations. In the present study we show that adenosine dialdehyde is also a potent inhibitor of vaccinia virus plaque formation in monolayer cultures of L cells. When added to the culture medium immediately following attachment of the virus, concentrations of the dialdehyde as low as 0.5 microM produce greater than 90% inhibition of plaque formation after 72 hr. The efficacy of the compound is greatest when added within 8 hr of virus attachment and gradually decreases in a time-dependent manner when added after this point. Treatment of L cells with 5 microM adenosine dialdehyde for 60 min prior to virus infection causes a transient, but virtually complete loss of S-adenosylhomocysteine hydrolase activity and subsequent 3-fold increase in the intracellular S-adenosylhomocysteine/S-adenosylmethionine ratio. Continuous exposure of infected cells to the dialdehyde results in prolonged inhibition of S-adenosylhomocysteine hydrolase accompanied by a 10-fold increase in the S-adenosylhomocysteine/S-adenosylmethionine ratio. Associated with these changes in the dialdehyde-treated, infected cells are an inhibition of early virus-specific protein synthesis and a 13% decrease in methylation of the cytoplasmic poly A+-mRNA. The antiviral action of this compound thus appears to be related to a decrease in viral mRNA methylation (e.g., the 5'-terminal cap structure) which results in suppressed translation of viral proteins essential for virus replication.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosylhomocysteinase,
http://linkedlifedata.com/resource/pubmed/chemical/Antiviral Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/Viral Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/periodate-oxidized adenosine
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0026-895X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
31
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
485-92
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:3574293-Adenosine,
pubmed-meshheading:3574293-Adenosylhomocysteinase,
pubmed-meshheading:3574293-Animals,
pubmed-meshheading:3574293-Antiviral Agents,
pubmed-meshheading:3574293-Hydrolases,
pubmed-meshheading:3574293-L Cells (Cell Line),
pubmed-meshheading:3574293-Methylation,
pubmed-meshheading:3574293-Mice,
pubmed-meshheading:3574293-RNA, Messenger,
pubmed-meshheading:3574293-RNA, Viral,
pubmed-meshheading:3574293-Vaccinia virus,
pubmed-meshheading:3574293-Viral Proteins,
pubmed-meshheading:3574293-Virus Replication
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pubmed:year |
1987
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pubmed:articleTitle |
Adenosine dialdehyde: a potent inhibitor of vaccinia virus multiplication in mouse L929 cells.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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