Linked Life Data

12757721

Source:http://linkedlifedata.com/resource/pubmed/id/12757721

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2003-5-21
pubmed:abstractText
In order to determine the importance of the two ester pharmacophores in high affinity, conformationally constrained DAG-lactones (Lac-1-5) as PK-C ligands, we have independently replaced the sn-1 and sn-2 carbonyl esters in these compounds by ketone (2, 10, 11), amide (3, 25-28), and hydroxyl (12, 13) isosteres. Although the ketone analogue of the sn-1 ester (2) exhibited comparable activity to the parent Lac-1 when taking into account the difference in lipophilicities, the other isosteres were significantly poorer PK-C alpha ligands compared to the parent DAG-lactones. This study demonstrates that the ester functionality in DAG-lactone plays an important role in the ligand's capacity to form a strong hydrogen bond with Gly253 at the active site. The discrete K(i) analysis from the sn-1 and sn-2 isosteres further confirms that the DAG-lactones bind preferentially to the C1-domain in the sn-2 binding mode, as previously suggested.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0968-0896
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2529-39
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Conformationally constrained analogues of diacylglycerol (DAG). Effect on protein kinase C (PK-C) binding by the isosteric replacement of sn-1 and sn-2 esters in DAG-lactones.
pubmed:affiliation
Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't