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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2004-2-2
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pubmed:abstractText |
Important questions remain regarding the impact of variations in the structure of the lipid A portion of lipopolysaccharide on activation of cells via the Toll-like receptor 4 complex. We have studied a series of synthetic lipid A mimetic compounds known as aminoalkyl glucosaminide phosphates in which the length of the secondary acyl chain has been systematically varied. Using transcriptional profiling of human monocytes and responses of Toll-like receptor 4 complex cell transfectants, we demonstrate a clear dependence of length on secondary acyl chain on Toll-like receptor 4 activation. Compounds with secondary acyl chains less than eight carbons in length have dramatically reduced activity, and substitutions of the left-sided secondary acyl chain had the most important effect on the Toll-like receptor 4 agonist activity of these molecules. The structure-function relationships of these compounds assessed via the induction of chemokines and cytokines following in vivo administration closely mirrored those seen with cell-based studies. This novel set of synthetic lipid A mimetics will be useful for Toll-like receptor 4-based investigations and may have clinical utility as stand-alone immunomodulators.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Lipid A,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/TLR4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:BaldridgeJory RJR,
pubmed-author:CluffChristopher WCW,
pubmed-author:Da Silva CorreiaJeanJ,
pubmed-author:ElliottMark WMW,
pubmed-author:EvansJay TJT,
pubmed-author:HershbergRobert MRM,
pubmed-author:JefferyEric WEW,
pubmed-author:JohnsonDavid ADA,
pubmed-author:LacyMichael JMJ,
pubmed-author:PersingDavid HDH,
pubmed-author:ProbstPeterP,
pubmed-author:StöverAxel GAG,
pubmed-author:UlevitchRichard JRJ
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4440-9
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:14570885-Adjuvants, Immunologic,
pubmed-meshheading:14570885-Animals,
pubmed-meshheading:14570885-Cytokines,
pubmed-meshheading:14570885-Gene Expression Profiling,
pubmed-meshheading:14570885-Humans,
pubmed-meshheading:14570885-Lipid A,
pubmed-meshheading:14570885-Macrophages,
pubmed-meshheading:14570885-Membrane Glycoproteins,
pubmed-meshheading:14570885-Mice,
pubmed-meshheading:14570885-Mice, Inbred BALB C,
pubmed-meshheading:14570885-Molecular Mimicry,
pubmed-meshheading:14570885-Monocytes,
pubmed-meshheading:14570885-Receptors, Cell Surface,
pubmed-meshheading:14570885-Structure-Activity Relationship,
pubmed-meshheading:14570885-Toll-Like Receptor 4,
pubmed-meshheading:14570885-Toll-Like Receptors,
pubmed-meshheading:14570885-Transcriptional Activation,
pubmed-meshheading:14570885-Tumor Necrosis Factor-alpha
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pubmed:year |
2004
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pubmed:articleTitle |
Structure-activity relationship of synthetic toll-like receptor 4 agonists.
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pubmed:affiliation |
Corixa Corporation, Seattle, Washington 98104, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, Non-P.H.S.
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