Source:http://linkedlifedata.com/resource/pubmed/id/10966739
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
17
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pubmed:dateCreated |
2000-9-21
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pubmed:abstractText |
In previous work, we have obtained potent protein kinase C (PK-C) ligands with low-namomolar binding affinities by constructing diacylglycerol (DAG) mimetics in which the sn-2 carbonyl of DAG was constrained into a lactone ring. An additional structural element that helped achieve high binding affinity was the presence of branched acyl or alpha-alkylidene chains. In the present study, the effects of similarly branched chains on a different lactone system, where the lactone carbonyl is now equivalent to the sn-1 carbonyl of DAG, are investigated. In this new lactone template, the two chiral centers must have the S-configuration for enzyme recognition. As with the sn-2 DAG lactones, the branched chains were designed to optimize van der Waals contacts with a group of conserved hydrophobic amino acids located on the rim of the C1 domain of PK-C. The acyl and alpha-alkylidene chains were also designed to be lipophilically equivalent (8 carbons each). Eight new compounds (7-14) representing all possible combinations of linear and branched acyl and alpha-alkylidene were synthesized and evaluated. The sn-1 DAG lactones were less effective as PK-C ligands than the sn-2 DAG lactones despite having a similar array of linear or branched acyl and alpha-alkylidene chains
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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/Diglycerides,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Lactones,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3209-17
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:10966739-Diglycerides,
pubmed-meshheading:10966739-Isoenzymes,
pubmed-meshheading:10966739-Lactones,
pubmed-meshheading:10966739-Ligands,
pubmed-meshheading:10966739-Molecular Mimicry,
pubmed-meshheading:10966739-Protein Binding,
pubmed-meshheading:10966739-Protein Kinase C,
pubmed-meshheading:10966739-Stereoisomerism,
pubmed-meshheading:10966739-Structure-Activity Relationship
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pubmed:year |
2000
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pubmed:articleTitle |
Conformationally constrained analogues of diacylglycerol (DAG). 17. Contrast between sn-1 and sn-2 DAG lactones in binding to protein kinase C.
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pubmed:affiliation |
Laboratories of Medicinal Chemistry and of Cellular Carcinogenesis and Tumor Promotion, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
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pubmed:publicationType |
Journal Article
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