Discovery of a quorum sensing modulator pharmacophore by 3D small-molecule microarray screening

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

Standard

Discovery of a quorum sensing modulator pharmacophore by 3D small-molecule microarray screening. / Marsden, David M; Nicholson, Rebecca L; Skindersoe, Mette E; Galloway, Warren R J D; Sore, Hannah F; Givskov, Michael; Salmond, George P C; Ladlow, Mark; Welch, Martin; Spring, David R.

In: Organic & Biomolecular Chemistry, Vol. 8, No. 23, 07.12.2010, p. 5313-23.

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

Harvard

Marsden, DM, Nicholson, RL, Skindersoe, ME, Galloway, WRJD, Sore, HF, Givskov, M, Salmond, GPC, Ladlow, M, Welch, M & Spring, DR 2010, 'Discovery of a quorum sensing modulator pharmacophore by 3D small-molecule microarray screening', Organic & Biomolecular Chemistry, vol. 8, no. 23, pp. 5313-23. https://doi.org/10.1039/c0ob00300j

APA

Marsden, D. M., Nicholson, R. L., Skindersoe, M. E., Galloway, W. R. J. D., Sore, H. F., Givskov, M., Salmond, G. P. C., Ladlow, M., Welch, M., & Spring, D. R. (2010). Discovery of a quorum sensing modulator pharmacophore by 3D small-molecule microarray screening. Organic & Biomolecular Chemistry, 8(23), 5313-23. https://doi.org/10.1039/c0ob00300j

Vancouver

Marsden DM, Nicholson RL, Skindersoe ME, Galloway WRJD, Sore HF, Givskov M et al. Discovery of a quorum sensing modulator pharmacophore by 3D small-molecule microarray screening. Organic & Biomolecular Chemistry. 2010 Dec 7;8(23):5313-23. https://doi.org/10.1039/c0ob00300j

Author

Marsden, David M ; Nicholson, Rebecca L ; Skindersoe, Mette E ; Galloway, Warren R J D ; Sore, Hannah F ; Givskov, Michael ; Salmond, George P C ; Ladlow, Mark ; Welch, Martin ; Spring, David R. / Discovery of a quorum sensing modulator pharmacophore by 3D small-molecule microarray screening. In: Organic & Biomolecular Chemistry. 2010 ; Vol. 8, No. 23. pp. 5313-23.

Bibtex

@article{a15f6e94ab8c48d6837c6eafc73ad8b0,
title = "Discovery of a quorum sensing modulator pharmacophore by 3D small-molecule microarray screening",
abstract = "The screening of large arrays of drug-like small-molecules was traditionally a time consuming and resource intensive task. New methodology developed within our laboratories provides an attractive low cost, 3D microarray-assisted screening platform that could be used to rapidly assay thousands of compounds. As a proof-of-principle the platform was exploited to screen a number of quorum sensing analogs. Quorum sensing is used by bacterium to initiate and spread infection; in this context its modulation may have significant clinical value. 3D microarray slides were probed with fluorescently labeled ligand-binding domains of the LuxR homolog CarR from Erwinia carotovora subsp. carotovora. The 3D microarray platform was used to discover the biologically active chloro-pyridine pharmacophore, which was validated using a fluorometric ligand binding assay and ITC. Analogs containing the chloro-pyridine pharmacophore were found to be potent inhibitors of N-acyl-homoserine-lactone (AHL) mediated quorum sensing phenotypes in Serratia (IC(50) = ~5 µM) and Pseudomonas aeruginosa (IC(50) = 10-20 µM).",
keywords = "Molecular Structure, Pectobacterium carotovorum, Quorum Sensing, Small Molecule Libraries",
author = "Marsden, {David M} and Nicholson, {Rebecca L} and Skindersoe, {Mette E} and Galloway, {Warren R J D} and Sore, {Hannah F} and Michael Givskov and Salmond, {George P C} and Mark Ladlow and Martin Welch and Spring, {David R}",
year = "2010",
month = dec,
day = "7",
doi = "10.1039/c0ob00300j",
language = "English",
volume = "8",
pages = "5313--23",
journal = "Organic & Biomolecular Chemistry",
issn = "1470-4358",
publisher = "Royal Society of Chemistry",
number = "23",

}

RIS

TY - JOUR

T1 - Discovery of a quorum sensing modulator pharmacophore by 3D small-molecule microarray screening

AU - Marsden, David M

AU - Nicholson, Rebecca L

AU - Skindersoe, Mette E

AU - Galloway, Warren R J D

AU - Sore, Hannah F

AU - Givskov, Michael

AU - Salmond, George P C

AU - Ladlow, Mark

AU - Welch, Martin

AU - Spring, David R

PY - 2010/12/7

Y1 - 2010/12/7

N2 - The screening of large arrays of drug-like small-molecules was traditionally a time consuming and resource intensive task. New methodology developed within our laboratories provides an attractive low cost, 3D microarray-assisted screening platform that could be used to rapidly assay thousands of compounds. As a proof-of-principle the platform was exploited to screen a number of quorum sensing analogs. Quorum sensing is used by bacterium to initiate and spread infection; in this context its modulation may have significant clinical value. 3D microarray slides were probed with fluorescently labeled ligand-binding domains of the LuxR homolog CarR from Erwinia carotovora subsp. carotovora. The 3D microarray platform was used to discover the biologically active chloro-pyridine pharmacophore, which was validated using a fluorometric ligand binding assay and ITC. Analogs containing the chloro-pyridine pharmacophore were found to be potent inhibitors of N-acyl-homoserine-lactone (AHL) mediated quorum sensing phenotypes in Serratia (IC(50) = ~5 µM) and Pseudomonas aeruginosa (IC(50) = 10-20 µM).

AB - The screening of large arrays of drug-like small-molecules was traditionally a time consuming and resource intensive task. New methodology developed within our laboratories provides an attractive low cost, 3D microarray-assisted screening platform that could be used to rapidly assay thousands of compounds. As a proof-of-principle the platform was exploited to screen a number of quorum sensing analogs. Quorum sensing is used by bacterium to initiate and spread infection; in this context its modulation may have significant clinical value. 3D microarray slides were probed with fluorescently labeled ligand-binding domains of the LuxR homolog CarR from Erwinia carotovora subsp. carotovora. The 3D microarray platform was used to discover the biologically active chloro-pyridine pharmacophore, which was validated using a fluorometric ligand binding assay and ITC. Analogs containing the chloro-pyridine pharmacophore were found to be potent inhibitors of N-acyl-homoserine-lactone (AHL) mediated quorum sensing phenotypes in Serratia (IC(50) = ~5 µM) and Pseudomonas aeruginosa (IC(50) = 10-20 µM).

KW - Molecular Structure

KW - Pectobacterium carotovorum

KW - Quorum Sensing

KW - Small Molecule Libraries

U2 - 10.1039/c0ob00300j

DO - 10.1039/c0ob00300j

M3 - Journal article

C2 - 20886127

VL - 8

SP - 5313

EP - 5323

JO - Organic & Biomolecular Chemistry

JF - Organic & Biomolecular Chemistry

SN - 1470-4358

IS - 23

ER -

ID: 33952311