Please use this identifier to cite or link to this item:
https://hdl.handle.net/10356/101266
Title: | Solid-Phase synthesis and biological evaluation of N-dipeptido L-homoserine lactones as quorum sensing activators | Authors: | Hansen, Mette R. Le Quement, Sebastian T. Jakobsen, Tim H. Skovstrup, Søren Taboureau, Olivier Tolker-Nielsen, Tim Givskov, Michael Nielsen, Thomas E. |
Keywords: | DRNTU::Science::Biological sciences | Issue Date: | 2014 | Source: | Hansen, M. R., Le Quement, S. T., Jakobsen, T. H., Skovstrup, S., Taboureau, O., Tolker-Nielsen, T., et al. (2014). Solid-Phase Synthesis and Biological Evaluation of N -Dipeptido L -Homoserine Lactones as Quorum Sensing Activators . ChemBioChem, 15(3), 460-465. | Series/Report no.: | ChemBioChem | Abstract: | Bacteria use small signaling molecules to communicate in a process termed “quorum sensing” (QS), which enables the coordination of survival strategies, such as production of virulence factors and biofilm formation. In Gram-negative bacteria, these signaling molecules are a series of N-acylated L-homoserine lactones. With the goal of identifying non-native compounds capable of modulating bacterial QS, a virtual library of N-dipeptido L-homoserine lactones was screened in silico with two different crystal structures of LasR. The 30 most promising hits were synthesized on HMBA-functionalized PEGA resin and released through an efficient acid-mediated cyclative release mechanism. Subsequent screening for modulation of QS in Pseudomonas aeruginosa and E. coli identified six moderately strong activators. A follow-up library designed from the preliminary derived structure–activity relationships was synthesized and evaluated for their ability to activate the QS system in this bacterium. This resulted in the identification of another six QS activators (two with low micromolar activity) thus illuminating structural features required for QS modulation. | URI: | https://hdl.handle.net/10356/101266 http://hdl.handle.net/10220/19692 |
ISSN: | 1439-4227 | DOI: | 10.1002/cbic.201300533 | Rights: | © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. | Fulltext Permission: | none | Fulltext Availability: | No Fulltext |
Appears in Collections: | SCELSE Journal Articles |
SCOPUSTM
Citations
50
5
Updated on Mar 21, 2024
Web of ScienceTM
Citations
50
5
Updated on Oct 31, 2023
Page view(s) 50
564
Updated on Mar 29, 2024
Google ScholarTM
Check
Altmetric
Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.