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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 <jats:italic>Shigella<\/jats:italic> T3SS tip protein IpaD is an attractive target for developing anti\u2010infectives 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\u2010molecule scaffolds that bind to IpaD, based on the methylquinoline, pyrrolidine\u2010aniline, 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\u2010molecule inhibitors of IpaD that could lead to new anti\u2010infectives.<\/jats:p>","DOI":"10.1002\/cmdc.201700348","type":"journal-article","created":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T13:58:40Z","timestamp":1501163920000},"page":"1534-1541","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Characterization of Small\u2010Molecule Scaffolds That Bind to the <i>Shigella<\/i> Type\u2005III Secretion System Protein IpaD"],"prefix":"10.1002","volume":"12","author":[{"given":"Supratim","family":"Dey","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences University of Kansas  1200 Sunnyside Avenue Lawrence KS 66045 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asokan","family":"Anbanandam","sequence":"additional","affiliation":[{"name":"Current address: Center for Drug Discovery and Innovation University of South Florida  3720 Spectrum Blvd., Suite #303 Tampa FL 33612 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben E.","family":"Mumford","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences University of Kansas  1200 Sunnyside Avenue Lawrence KS 66045 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1172-2917","authenticated-orcid":false,"given":"Roberto N.","family":"De\u2005Guzman","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences University of Kansas  1200 Sunnyside Avenue Lawrence KS 66045 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,8,31]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/S1473-3099(15)00003-1","volume":"15","author":"Agaisse H.","year":"2015","journal-title":"Lancet Infect. 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