Identification of LasR ligands through a virtual screening approach
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 a...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2014
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/101701 http://hdl.handle.net/10220/19785 |
| _version_ | 1826115037539860480 |
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| author | Skovstrup, Søren Le Quement, Sebastian Thordal Hansen, Thomas Jakobsen, Tim Holm Harmsen, Morten Tolker-Nielsen, Tim Nielsen, Thomas E. Givskov, Michael Taboureau, Olivier |
| author_facet | Skovstrup, Søren Le Quement, Sebastian Thordal Hansen, Thomas Jakobsen, Tim Holm Harmsen, Morten Tolker-Nielsen, Tim Nielsen, Thomas E. Givskov, Michael Taboureau, Olivier |
| author_sort | Skovstrup, Søren |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T03:48:39Z |
| format | Journal Article |
| id | ntu-10356/101701 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:48:39Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | ntu-10356/1017012020-03-07T12:47:11Z 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 DRNTU::Science::Medicine::Biomedical engineering 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. 2014-06-16T03:31:22Z 2019-12-06T20:43:01Z 2014-06-16T03:31:22Z 2019-12-06T20:43:01Z 2013 2013 Journal Article Skovstrup, S., Le Quement, S. T., Hansen, T., Jakobsen, T. H., Harmsen, M., Tolker-Nielsen, T., et al. (2013). Identification of LasR Ligands through a Virtual Screening Approach. ChemMedChem, 8(1), 157-163. 1860-7179 https://hdl.handle.net/10356/101701 http://hdl.handle.net/10220/19785 10.1002/cmdc.201200434 en ChemMedChem © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
| spellingShingle | DRNTU::Science::Medicine::Biomedical engineering 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 |
| title | Identification of LasR ligands through a virtual screening approach |
| title_full | Identification of LasR ligands through a virtual screening approach |
| title_fullStr | Identification of LasR ligands through a virtual screening approach |
| title_full_unstemmed | Identification of LasR ligands through a virtual screening approach |
| title_short | Identification of LasR ligands through a virtual screening approach |
| title_sort | identification of lasr ligands through a virtual screening approach |
| topic | DRNTU::Science::Medicine::Biomedical engineering |
| url | https://hdl.handle.net/10356/101701 http://hdl.handle.net/10220/19785 |
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