Abstract
A series of 15 racemic alkyl- and aryl-N-substituted ureas, derived from homoserine lactone, were synthesized and tested for their ability to competitively inhibit the action of 3-oxohexanoyl-l-homoserine lactone, the natural inducer of bioluminescence in the bacterium Vibrio fischeri. N-alkyl ureas with an alkyl chain of at least 4 carbon atoms, as well as certain ureas bearing a phenyl group at the extremity of the alkyl chain, were found to be significant antagonists. In the case of N-butyl urea, it has been shown that the antagonist activity was related to the inhibition of the dimerisation of the N-terminal domain of ExpR, a protein of the receptor LuxR family. Molecular modelling suggested that this would result from the formation of an additional hydrogen bond in the protein acylhomoserine lactone binding cavity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4-Butyrolactone / analogs & derivatives
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4-Butyrolactone / chemical synthesis
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4-Butyrolactone / chemistry
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4-Butyrolactone / pharmacology
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Aliivibrio fischeri / drug effects*
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Aliivibrio fischeri / genetics
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Aliivibrio fischeri / metabolism*
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Base Sequence
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Binding Sites
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DNA, Bacterial / genetics
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Dimerization
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Luminescence
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Models, Molecular
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Protein Structure, Tertiary
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Repressor Proteins / antagonists & inhibitors*
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Repressor Proteins / chemistry
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Trans-Activators / antagonists & inhibitors*
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Urea / analogs & derivatives*
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Urea / chemical synthesis
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Urea / chemistry
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Urea / pharmacology
Substances
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DNA, Bacterial
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Repressor Proteins
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Trans-Activators
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LuxR autoinducer binding proteins
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homoserine lactone
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Urea
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4-Butyrolactone