Solid-phase synthesis and biological evaluation of N-dipeptido L-homoserine lactones as quorum sensing activators

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Standard

Solid-phase synthesis and biological evaluation of N-dipeptido L-homoserine lactones as quorum sensing activators. / Hansen, Mette R; Le Quement, Sebastian T; Jakobsen, Tim H; Skovstrup, Søren; Taboureau, Olivier; Tolker-Nielsen, Tim; Givskov, Michael; Nielsen, Thomas E.

In: ChemBioChem, Vol. 15, No. 3, 10.02.2014, p. 460-5.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Hansen, MR, Le Quement, ST, Jakobsen, TH, Skovstrup, S, Taboureau, O, Tolker-Nielsen, T, Givskov, M & Nielsen, TE 2014, 'Solid-phase synthesis and biological evaluation of N-dipeptido L-homoserine lactones as quorum sensing activators', ChemBioChem, vol. 15, no. 3, pp. 460-5. https://doi.org/10.1002/cbic.201300533

APA

Hansen, M. R., Le Quement, S. T., Jakobsen, T. H., Skovstrup, S., Taboureau, O., Tolker-Nielsen, T., Givskov, M., & Nielsen, T. E. (2014). Solid-phase synthesis and biological evaluation of N-dipeptido L-homoserine lactones as quorum sensing activators. ChemBioChem, 15(3), 460-5. https://doi.org/10.1002/cbic.201300533

Vancouver

Hansen MR, Le Quement ST, Jakobsen TH, Skovstrup S, Taboureau O, Tolker-Nielsen T et al. Solid-phase synthesis and biological evaluation of N-dipeptido L-homoserine lactones as quorum sensing activators. ChemBioChem. 2014 Feb 10;15(3):460-5. https://doi.org/10.1002/cbic.201300533

Author

Hansen, Mette R ; Le Quement, Sebastian T ; Jakobsen, Tim H ; Skovstrup, Søren ; Taboureau, Olivier ; Tolker-Nielsen, Tim ; Givskov, Michael ; Nielsen, Thomas E. / Solid-phase synthesis and biological evaluation of N-dipeptido L-homoserine lactones as quorum sensing activators. In: ChemBioChem. 2014 ; Vol. 15, No. 3. pp. 460-5.

Bibtex

@article{c324510272bb463eaac7c77e7eb3ce23,
title = "Solid-phase synthesis and biological evaluation of N-dipeptido L-homoserine lactones as quorum sensing activators",
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.",
keywords = "Acyl-Butyrolactones, Bacterial Proteins, Binding Sites, Dipeptides, Molecular Docking Simulation, Protein Binding, Protein Structure, Tertiary, Pseudomonas aeruginosa, Quorum Sensing, Solid-Phase Synthesis Techniques, Trans-Activators",
author = "Hansen, {Mette R} and {Le Quement}, {Sebastian T} and Jakobsen, {Tim H} and S{\o}ren Skovstrup and Olivier Taboureau and Tim Tolker-Nielsen and Michael Givskov and Nielsen, {Thomas E}",
note = "Copyright {\textcopyright} 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
year = "2014",
month = feb,
day = "10",
doi = "10.1002/cbic.201300533",
language = "English",
volume = "15",
pages = "460--5",
journal = "ChemBioChem",
issn = "1439-4227",
publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",
number = "3",

}

RIS

TY - JOUR

T1 - Solid-phase synthesis and biological evaluation of N-dipeptido L-homoserine lactones as quorum sensing activators

AU - Hansen, Mette R

AU - Le Quement, Sebastian T

AU - Jakobsen, Tim H

AU - Skovstrup, Søren

AU - Taboureau, Olivier

AU - Tolker-Nielsen, Tim

AU - Givskov, Michael

AU - Nielsen, Thomas E

N1 - Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2014/2/10

Y1 - 2014/2/10

N2 - 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.

AB - 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.

KW - Acyl-Butyrolactones

KW - Bacterial Proteins

KW - Binding Sites

KW - Dipeptides

KW - Molecular Docking Simulation

KW - Protein Binding

KW - Protein Structure, Tertiary

KW - Pseudomonas aeruginosa

KW - Quorum Sensing

KW - Solid-Phase Synthesis Techniques

KW - Trans-Activators

U2 - 10.1002/cbic.201300533

DO - 10.1002/cbic.201300533

M3 - Journal article

C2 - 24436223

VL - 15

SP - 460

EP - 465

JO - ChemBioChem

JF - ChemBioChem

SN - 1439-4227

IS - 3

ER -

ID: 129018641