New synthetic analogues of N-acyl homoserine lactones as agonists or antagonists of transcriptional regulators involved in bacterial quorum sensing.
A series of 22 novel synthetic N-acyl-homoserine lactone analogues has been evaluated for both their inducing activity and their ability to competitively inhibit the action of 3-oxo-hexanoyl-L-homoserine lactone, the natural inducer of bioluminescence in the bacterium Vibrio fischeri. In the newly synthesized analogues, the extremity of the acyl chain was modified by introducing ramified alkyl, cycloalkyl or aryl substituents at the C-4 position. Most of the analogues bearing either acyclic or cyclic alkyl substituents showed inducing activity. In contrast, the phenyl substituted analogues displayed significant antagonist activity. We hypothesized that the antagonist activity of the phenyl compounds may result from the interaction between the aryl group and aromatic amino acids of the LuxR receptor, preventing it from adopting the active dimeric form.
Reverchon
Sylvie
S
Unité de Microbiologie et Génétique CNRS-INSA-UCB UMR 5122, INSA, Batiment Louis Pasteur, 11 Avenue Jean Capelle, 69621, Villeurbanne, France. reverchon@insa-lyon.fr
Chantegrel
Bernard
B
Deshayes
Christian
C
Doutheau
Alain
A
Cotte-Pattat
Nicole
N
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D012097:Repressor Proteins / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D014733:Vibrio / Q000235:genetics / Q000502:physiology
D001426:Bacterial Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; C064778:LuxR autoinducer binding proteins; C088386:homoserine lactone; D015107:4-Butyrolactone