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Title: Indoline-6-Sulfonamide Inhibitors of the Bacterial Enzyme DapE

Abstract

Inhibitors of the bacterial enzyme dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE; EC 3.5.1.18) hold promise as antibiotics with a new mechanism of action. Herein we describe the discovery of a new series of indoline sulfonamide DapE inhibitors from a high-throughput screen and the synthesis of a series of analogs. Inhibitory potency was measured by a ninhydrin-based DapE assay recently developed by our group. Molecular docking experiments suggest active site binding with the sulfonamide acting as a zinc-binding group (ZBG).

Authors:
 [1];  [2];  [2]; ORCiD logo [2];  [2];  [2];  [3];  [2];  [4]; ORCiD logo [2]
+ Show Author Affiliations
  1. Loyola Univ., Chicago, IL (United States); Northwestern Univ., Evanston, IL (United States)
  2. Loyola Univ., Chicago, IL (United States)
  3. Argonne National Lab. (ANL), Argonne, IL (United States)
  4. Colorado School of Mines, Golden, CO (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH); National Science Foundation (NSF)
OSTI Identifier:
1764848
Grant/Contract Number:  
AC02-06CH11357; HHSN272200700058C; HHSN272201200026C; CHE-1412443
Resource Type:
Accepted Manuscript
Journal Name:
Antibiotics
Additional Journal Information:
Journal Volume: 9; Journal Issue: 9; Journal ID: ISSN 2079-6382
Publisher:
MDPI
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; DapE; antibiotic; diaminopimelate desuccinylase; enzyme inhibition; indoline; ninhydrin enzyme assay; sulfonamide

Citation Formats

Reidl, Cory T., Heath, Tahirah K., Darwish, Iman, Torrez, Rachel M., Moore, Maxwell, Gild, Elliot, Nocek, Boguslaw P., Starus, Anna, Holz, Richard C., and Becker, Daniel P. Indoline-6-Sulfonamide Inhibitors of the Bacterial Enzyme DapE. United States: N. p., 2020. Web. doi:10.3390/antibiotics9090595.
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Reidl, Cory T., Heath, Tahirah K., Darwish, Iman, Torrez, Rachel M., Moore, Maxwell, Gild, Elliot, Nocek, Boguslaw P., Starus, Anna, Holz, Richard C., & Becker, Daniel P. Indoline-6-Sulfonamide Inhibitors of the Bacterial Enzyme DapE. United States. https://doi.org/10.3390/antibiotics9090595
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Reidl, Cory T., Heath, Tahirah K., Darwish, Iman, Torrez, Rachel M., Moore, Maxwell, Gild, Elliot, Nocek, Boguslaw P., Starus, Anna, Holz, Richard C., and Becker, Daniel P. Fri . "Indoline-6-Sulfonamide Inhibitors of the Bacterial Enzyme DapE". United States. https://doi.org/10.3390/antibiotics9090595. https://www.osti.gov/servlets/purl/1764848.
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@article{osti_1764848,
title = {Indoline-6-Sulfonamide Inhibitors of the Bacterial Enzyme DapE},
author = {Reidl, Cory T. and Heath, Tahirah K. and Darwish, Iman and Torrez, Rachel M. and Moore, Maxwell and Gild, Elliot and Nocek, Boguslaw P. and Starus, Anna and Holz, Richard C. and Becker, Daniel P.},
abstractNote = {Inhibitors of the bacterial enzyme dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE; EC 3.5.1.18) hold promise as antibiotics with a new mechanism of action. Herein we describe the discovery of a new series of indoline sulfonamide DapE inhibitors from a high-throughput screen and the synthesis of a series of analogs. Inhibitory potency was measured by a ninhydrin-based DapE assay recently developed by our group. Molecular docking experiments suggest active site binding with the sulfonamide acting as a zinc-binding group (ZBG).},
doi = {10.3390/antibiotics9090595},
journal = {Antibiotics},
number = 9,
volume = 9,
place = {United States},
year = {Fri Sep 11 00:00:00 EDT 2020},
month = {Fri Sep 11 00:00:00 EDT 2020}
}
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Journal Article:
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Publisher's Version of Record
https://doi.org/10.3390/antibiotics9090595
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