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Characterization of Small‐Molecule Scaffolds That Bind to the Shigella Type III Secretion System Protein IpaD
Author(s) -
Dey Supratim,
Anbanandam Asokan,
Mumford Ben E.,
De Guzman Roberto N.
Publication year - 2017
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700348
Subject(s) - virulence , shigella , type three secretion system , small molecule , microbiology and biotechnology , secretion , chemistry , effector , bacteria , biology , biochemistry , escherichia coli , genetics , gene
Many pathogens such as Shigella and other bacteria assemble the type III secretion system (T3SS) nanoinjector to inject virulence proteins into their target cells to cause infectious diseases in humans. The rise of drug resistance among pathogens that rely on the T3SS for infectivity, plus the dearth of new antibiotics require alternative strategies in developing new antibiotics. The Shigella T3SS tip protein IpaD is an attractive target for developing anti‐infectives because of its essential role in virulence and its exposure on the bacterial surface. Currently, the only known small molecules that bind to IpaD are bile salt sterols. In this study we identified four new small‐molecule scaffolds that bind to IpaD, based on the methylquinoline, pyrrolidine‐aniline, hydroxyindole, and morpholinoaniline scaffolds. NMR mapping revealed potential hotspots in IpaD for binding small molecules. These scaffolds can be used as building blocks in developing small‐molecule inhibitors of IpaD that could lead to new anti‐infectives.