Open Access
Journal of Medicinal Chemistry, volume 57, issue 6, pages 2799-2806
Discovery of Lead Compounds Targeting the Bacterial Sliding Clamp Using a Fragment-Based Approach
Yin Zhou-Ping
1
,
Whittell Louise R
1
,
Wang Yao
1
,
Jergic Slobodan
1
,
Liu M.
2
,
Harry Elizabeth J.
2
,
Dixon N. E.
1
,
Beck Jennifer L.
1
,
Kelso Michael J.
1
,
Oakley Aaron J.
1
1
School
of Chemistry and Centre for Medical and Molecular Bioscience, University of Wollongong, Wollongong, New South Wales 2522, Australia
|
Publication type: Journal Article
Publication date: 2014-03-18
Journal:
Journal of Medicinal Chemistry
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 7.3
ISSN: 00222623, 15204804
Drug Discovery
Molecular Medicine
Abstract
The bacterial sliding clamp (SC), also known as the DNA polymerase III β subunit, is an emerging antibacterial target that plays a central role in DNA replication, serving as a protein-protein interaction hub with a common binding pocket to recognize linear motifs in the partner proteins. Here, fragment-based screening using X-ray crystallography produced four hits bound in the linear-motif-binding pocket of the Escherichia coli SC. Compounds structurally related to the hits were identified that inhibited the E. coli SC and SC-mediated DNA replication in vitro. A tetrahydrocarbazole derivative emerged as a promising lead whose methyl and ethyl ester prodrug forms showed minimum inhibitory concentrations in the range of 21-43 μg/mL against representative Gram-negative and Gram-positive bacteria species. The work demonstrates the utility of a fragment-based approach for identifying bacterial sliding clamp inhibitors as lead compounds with broad-spectrum antibacterial activity.
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Citations by publishers
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12
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1 publication, 2.27%
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1 publication, 2.27%
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American Association for the Advancement of Science (AAAS)
1 publication, 2.27%
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1 publication, 2.27%
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1 publication, 2.27%
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2
4
6
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12
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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RIS |
BibTex |
MLA
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GOST
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Yin Z. et al. Discovery of Lead Compounds Targeting the Bacterial Sliding Clamp Using a Fragment-Based Approach // Journal of Medicinal Chemistry. 2014. Vol. 57. No. 6. pp. 2799-2806.
GOST all authors (up to 50)
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Yin Z., Whittell L. R., Wang Y., Jergic S., Liu M., Harry E. J., Dixon N. E., Beck J. L., Kelso M. J., Oakley A. J. Discovery of Lead Compounds Targeting the Bacterial Sliding Clamp Using a Fragment-Based Approach // Journal of Medicinal Chemistry. 2014. Vol. 57. No. 6. pp. 2799-2806.
Cite this
RIS
Copy
TY - JOUR
DO - 10.1021/jm500122r
UR - https://doi.org/10.1021%2Fjm500122r
TI - Discovery of Lead Compounds Targeting the Bacterial Sliding Clamp Using a Fragment-Based Approach
T2 - Journal of Medicinal Chemistry
AU - Whittell, Louise R
AU - Yin, Zhou-Ping
AU - Wang, Yao
AU - Jergic, Slobodan
AU - Liu, M.
AU - Harry, Elizabeth J.
AU - Dixon, N. E.
AU - Beck, Jennifer L.
AU - Kelso, Michael J.
AU - Oakley, Aaron J.
PY - 2014
DA - 2014/03/18 00:00:00
PB - American Chemical Society (ACS)
SP - 2799-2806
IS - 6
VL - 57
SN - 0022-2623
SN - 1520-4804
ER -
Cite this
BibTex
Copy
@article{2014_Yin,
author = {Louise R Whittell and Zhou-Ping Yin and Yao Wang and Slobodan Jergic and M. Liu and Elizabeth J. Harry and N. E. Dixon and Jennifer L. Beck and Michael J. Kelso and Aaron J. Oakley},
title = {Discovery of Lead Compounds Targeting the Bacterial Sliding Clamp Using a Fragment-Based Approach},
journal = {Journal of Medicinal Chemistry},
year = {2014},
volume = {57},
publisher = {American Chemical Society (ACS)},
month = {mar},
url = {https://doi.org/10.1021%2Fjm500122r},
number = {6},
pages = {2799--2806},
doi = {10.1021/jm500122r}
}
Cite this
MLA
Copy
Yin, Zhou-Ping, et al. “Discovery of Lead Compounds Targeting the Bacterial Sliding Clamp Using a Fragment-Based Approach.” Journal of Medicinal Chemistry, vol. 57, no. 6, Mar. 2014, pp. 2799-2806. https://doi.org/10.1021%2Fjm500122r.