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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
17
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pubmed:dateCreated |
2008-9-8
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pubmed:abstractText |
Using a diacylglycerol-lactone (DAG-lactone) template previously developed in our laboratory as a scaffold with high binding affinity for C1 domains, we describe herein a series of novel DAG-lactones containing heterocyclic moieties (pyridines, quinolines, and indoles) as alpha-arylidene fragments. Some of the DAG-lactones obtained show selective binding to RasGRP3 as compared to PKCalpha by more than 2 orders of magnitude and possess subnanomolar affinities. Because activated C1 domains bound to their ligands (DAG or DAG-lactones) insert into membranes, the lipid composition of membranes (cellular, nuclear, and those of internal organelles) is an important determinant for specificity. Therefore, reaching a proper hydrophilic/lipophilic balance for these molecules is critical. This was achieved by carefully selecting partnering acyl fragments for the DAG-lactones with the appropriate lipophilicity. The results clearly show that the combination of chemical and physical properties in these molecules needs to be perfectly balanced to achieve the desired specificity.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-10506570,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-10715158,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-10851170,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-11395409,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-12414987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-12801241,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-12809530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-1411571,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-14755890,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-15032665,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-15212759,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-15228292,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-15667202,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-15923197,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-16722637,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-18263588,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-3486050,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-526298,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-7664052,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-7781068,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-8496137,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-9191157,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-9271501,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-9582122,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18707088-9875475
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1520-4804
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
11
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pubmed:volume |
51
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5371-86
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
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pubmed:year |
2008
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pubmed:articleTitle |
Conformationally constrained analogues of diacylglycerol. 30. An investigation of diacylglycerol-lactones containing heteroaryl groups reveals compounds with high selectivity for Ras guanyl nucleotide-releasing proteins.
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pubmed:affiliation |
Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, 376 Boyles Street, Frederick, Maryland 21702, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Intramural
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