202284-85-3Relevant articles and documents
Thiolactone modulators of quorum sensing revealed through library design and screening
McInnis, Christine E.,Blackwell, Helen E.
, p. 4820 - 4828 (2011)
Quorum sensing (QS) is a process by which bacteria use small molecules or peptidic signals to assess their local population densities. At sufficiently high density, bacteria can alter gene expression levels to regulate group behaviors involved in a range of important and diverse phenotypes, including virulence factor production, biofilm formation, root nodulation, and bioluminescence. Gram-negative bacteria most commonly use N-acylated l-homoserine lactones (AHLs) as their QS signals. The AHL lactone ring is hydrolyzed relatively rapidly at biological pH, and the ring-opened product is QS inactive. We seek to identify AHL analogues with heightened hydrolytic stability, and thereby potentially heightened activity, for use as non-native modulators of bacterial QS. As part of this effort, we probed the utility of thiolactone analogues in the current study as QS agonists and antagonists in Gram-negative bacteria. A focused library of thiolactone analogs was designed and rapidly synthesized in solution. We examined the activity of the library as agonists and antagonists of LuxR-type QS receptors in Pseudomonas aeruginosa (LasR), Vibrio fischeri (LuxR), and Agrobacterium tumefaciens (TraR) using bacterial reporter strains. The thiolactone library contained several highly active compounds, including some of the most active LuxR inhibitors and the most active synthetic TraR agonist reported to date. Analysis of a representative thiolactone analog revealed that its hydrolysis half-life was almost double that of its parent AHL in bacterial growth medium.
The synthesis of optically pure enantiomers of N-Acyl-homoserine lactone autoinducers and their analogues
Ikeda, Tsukasa,Kajiyama, Koshiro,Kita, Toshikazu,Takiguchi, Noboru,Kuroda, Akio,Kato, Junichi,Ohtake, Hisao
, p. 314 - 315 (2007/10/03)
Optically pure enantiomers of N-acyl-homoserine lactones and thiolactones, whose optical purities were unambiguously determined by chiral stationary phase HPLC analyses, were firstly synthesized. Bioassays revealed that L-isomers were essential as the aut
