Identification of LasR ligands through a virtual screening approach

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

Standard

Identification of LasR ligands through a virtual screening approach. / Skovstrup, Søren; Le Quement, Sebastian Thordal; Hansen, Thomas; Jakobsen, Tim Holm; Harmsen, Morten; Tolker-Nielsen, Tim; Nielsen, Thomas E; Givskov, Michael; Taboureau, Olivier.

In: ChemMedChem, Vol. 8, No. 1, 2013, p. 157-63.

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

Harvard

Skovstrup, S, Le Quement, ST, Hansen, T, Jakobsen, TH, Harmsen, M, Tolker-Nielsen, T, Nielsen, TE, Givskov, M & Taboureau, O 2013, 'Identification of LasR ligands through a virtual screening approach', ChemMedChem, vol. 8, no. 1, pp. 157-63. https://doi.org/10.1002/cmdc.201200434

APA

Skovstrup, S., Le Quement, S. T., Hansen, T., Jakobsen, T. H., Harmsen, M., Tolker-Nielsen, T., Nielsen, T. E., Givskov, M., & Taboureau, O. (2013). Identification of LasR ligands through a virtual screening approach. ChemMedChem, 8(1), 157-63. https://doi.org/10.1002/cmdc.201200434

Vancouver

Skovstrup S, Le Quement ST, Hansen T, Jakobsen TH, Harmsen M, Tolker-Nielsen T et al. Identification of LasR ligands through a virtual screening approach. ChemMedChem. 2013;8(1):157-63. https://doi.org/10.1002/cmdc.201200434

Author

Skovstrup, Søren ; Le Quement, Sebastian Thordal ; Hansen, Thomas ; Jakobsen, Tim Holm ; Harmsen, Morten ; Tolker-Nielsen, Tim ; Nielsen, Thomas E ; Givskov, Michael ; Taboureau, Olivier. / Identification of LasR ligands through a virtual screening approach. In: ChemMedChem. 2013 ; Vol. 8, No. 1. pp. 157-63.

Bibtex

@article{13e3cac425244a53a00eae27eb3d1b1f,
title = "Identification of LasR ligands through a virtual screening approach",
abstract = "With the widespread occurrence of bacterial resistance to antibiotics, the development of new strategies beyond conventional treatments is a pursuit taken by public health institutions worldwide. LasR, a transcription factor that controls quorum sensing in Pseudomonas aeruginosa, has emerged as an attractive therapeutic target for the next generation of antimicrobial agents. In the present study, a virtual screening workflow combining pharmacophore- and structure-based approaches was used to identify new LasR ligands. Five novel inducers and three inhibitors of LasR activity were validated experimentally by use of a cell-based assay. Interestingly, these compounds are molecularly distinct from the native signal molecule, N-3-oxododecanoyl-L-homoserine lactone (OHN), and may serve as lead structures for the design of new drugs. The binding modes of these compounds to the OHN binding site in LasR were predicted and used to identify the key interactions that contribute to the induction and inhibition of LasR activity.",
author = "S{\o}ren Skovstrup and {Le Quement}, {Sebastian Thordal} and Thomas Hansen and Jakobsen, {Tim Holm} and Morten Harmsen and Tim Tolker-Nielsen and Nielsen, {Thomas E} and Michael Givskov and Olivier Taboureau",
note = "Copyright {\textcopyright} 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
year = "2013",
doi = "10.1002/cmdc.201200434",
language = "English",
volume = "8",
pages = "157--63",
journal = "Farmaco",
issn = "1860-7179",
publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",
number = "1",

}

RIS

TY - JOUR

T1 - Identification of LasR ligands through a virtual screening approach

AU - Skovstrup, Søren

AU - Le Quement, Sebastian Thordal

AU - Hansen, Thomas

AU - Jakobsen, Tim Holm

AU - Harmsen, Morten

AU - Tolker-Nielsen, Tim

AU - Nielsen, Thomas E

AU - Givskov, Michael

AU - Taboureau, Olivier

N1 - Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2013

Y1 - 2013

N2 - With the widespread occurrence of bacterial resistance to antibiotics, the development of new strategies beyond conventional treatments is a pursuit taken by public health institutions worldwide. LasR, a transcription factor that controls quorum sensing in Pseudomonas aeruginosa, has emerged as an attractive therapeutic target for the next generation of antimicrobial agents. In the present study, a virtual screening workflow combining pharmacophore- and structure-based approaches was used to identify new LasR ligands. Five novel inducers and three inhibitors of LasR activity were validated experimentally by use of a cell-based assay. Interestingly, these compounds are molecularly distinct from the native signal molecule, N-3-oxododecanoyl-L-homoserine lactone (OHN), and may serve as lead structures for the design of new drugs. The binding modes of these compounds to the OHN binding site in LasR were predicted and used to identify the key interactions that contribute to the induction and inhibition of LasR activity.

AB - With the widespread occurrence of bacterial resistance to antibiotics, the development of new strategies beyond conventional treatments is a pursuit taken by public health institutions worldwide. LasR, a transcription factor that controls quorum sensing in Pseudomonas aeruginosa, has emerged as an attractive therapeutic target for the next generation of antimicrobial agents. In the present study, a virtual screening workflow combining pharmacophore- and structure-based approaches was used to identify new LasR ligands. Five novel inducers and three inhibitors of LasR activity were validated experimentally by use of a cell-based assay. Interestingly, these compounds are molecularly distinct from the native signal molecule, N-3-oxododecanoyl-L-homoserine lactone (OHN), and may serve as lead structures for the design of new drugs. The binding modes of these compounds to the OHN binding site in LasR were predicted and used to identify the key interactions that contribute to the induction and inhibition of LasR activity.

U2 - 10.1002/cmdc.201200434

DO - 10.1002/cmdc.201200434

M3 - Journal article

C2 - 23203920

VL - 8

SP - 157

EP - 163

JO - Farmaco

JF - Farmaco

SN - 1860-7179

IS - 1

ER -

ID: 44311000