Design, synthesis, and biological evaluation of abiotic, non-lactone modulators of LuxR-type quorum sensing.
Bioorg Med Chem
; 19(16): 4812-9, 2011 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-21798749
ABSTRACT
Quorum sensing (QS) is a cell-cell signaling mechanism that allows bacteria to monitor their population size and alter their behavior at high cell densities. Gram-negative bacteria use N-acylated L-homoserine lactones (AHLs) as their primary signals for QS. These signals are susceptible to lactone hydrolysis in biologically relevant media, and the ring-opened products are inactive QS signals. We have previously identified a range of non-native AHLs capable of strongly agonizing and antagonizing QS in Gram-negative bacteria. However, these abiotic AHLs are also prone to hydrolysis and inactivation and thereby have a relatively short time window for use (â¼12-48 h). Non-native QS modulators with reduced or no hydrolytic instability could have enhanced potencies and would be valuable as tools to study the mechanisms of QS in a range of environments (for example, on eukaryotic hosts). This study reports the design and synthesis of two libraries of new, non-hydrolyzable AHL mimics. The libraries were screened for QS modulatory activity using LasR, LuxR, and TraR bacterial reporter strains, and several new, abiotic agonists and antagonists of these receptors were identified.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Desenho de Fármacos
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Transativadores
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Percepção de Quorum
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Acil-Butirolactonas
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Bactérias Gram-Negativas
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Bioorg Med Chem
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos