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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
1987-12-9
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pubmed:abstractText |
Inhibitors 1-4 have been shown previously to undergo enzymatic phosphorylation by glutamine synthetase (GS). Phosphonates 6-9 were designed as chemically stable analogues of these phosphorylated inhibitors, incorporating either a tetrahedral sulfur group (6-8) (-S-, -SO-, -SO2-) or phosphinate (9) adjacent to methylphosphonic acid. Phosphonates 6-8 resemble the transiently stable phosphorylated methionine sulfone (2), whereas 9 resembles phosphorylated 2-amino-4-phosphonobutyric acid (4). When tested as inhibitors of glutamine synthetase from bacteria, mammals, and plants, analogue 9 proved to be the most potent, with a Ki value of 7.5 X 10(-5) M vs. the Escherichia coli enzyme. Analysis of the inhibition data for 6-9 suggests that a replacement of the oxygen bridging the tetrahedral sulfur (6-8) or phosphinate (9) and the terminal phosphate with a hydrophobic methylene drastically reduces the enzyme's affinity for inhibitors. Enhanced affinity of GS for phosphonate 9 may result from interaction of the negative charge on the phosphinate with Mn2+ at the active site.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2062-7
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading | |
pubmed:year |
1987
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pubmed:articleTitle |
Design and synthesis of phosphonate inhibitors of glutamine synthetase.
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pubmed:affiliation |
Department of Chemistry, Pennsylvania State University, University Park 16802.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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