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Aminoacyl\u2010tRNA synthetases (ARSs) are essential enzymes and well\u2010established antibacterial targets and so constitute a promising set of targets for the development of new antimalarials. Despite their potential as drug targets, apicoplastic ARSs remain unexplored. We have characterized the lysylation system of <jats:italic>Plasmodium falciparum<\/jats:italic>, and designed, synthesized, and tested a set of inhibitors based on the structure of the natural substrate intermediate: lysyl\u2010adenylate. Here we demonstrate that selective inhibition of apicoplastic ARSs is feasible and describe new compounds that that specifically inhibit <jats:italic>Plasmodium<\/jats:italic> apicoplastic lysyl\u2010tRNA synthetase and show antimalarial activities in the micromolar range.<\/jats:p>","DOI":"10.1002\/cbic.201200620","type":"journal-article","created":{"date-parts":[[2013,2,27]],"date-time":"2013-02-27T05:47:31Z","timestamp":1361944051000},"page":"499-509","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Selective Inhibition of an Apicoplastic Aminoacyl\u2010tRNA Synthetase from <i>Plasmodium falciparum<\/i>"],"prefix":"10.1002","volume":"14","author":[{"given":"Rob","family":"Hoen","sequence":"first","affiliation":[]},{"given":"Eva Maria","family":"Novoa","sequence":"additional","affiliation":[]},{"given":"Alba","family":"L\u00f3pez","sequence":"additional","affiliation":[]},{"given":"Noelia","family":"Camacho","sequence":"additional","affiliation":[]},{"given":"Laia","family":"Cubells","sequence":"additional","affiliation":[]},{"given":"Pedro","family":"Vieira","sequence":"additional","affiliation":[]},{"given":"Manuel","family":"Santos","sequence":"additional","affiliation":[]},{"given":"Patricia","family":"Marin\u2010Garcia","sequence":"additional","affiliation":[]},{"given":"Jose Maria","family":"Bautista","sequence":"additional","affiliation":[]},{"given":"Alfred","family":"Cort\u00e9s","sequence":"additional","affiliation":[]},{"given":"Llu\u00eds","family":"Ribas de Pouplana","sequence":"additional","affiliation":[]},{"given":"Miriam","family":"Royo","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2013,2,27]]},"reference":[{"key":"e_1_2_6_1_2","unstructured":"World Malaria Report 2010 http:\/\/www.who.int\/malaria\/world_malaria_report_2010\/en\/index.html."},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2011.04.042"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01099"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01097"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01094"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01095"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01102"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01111"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01107"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2009.0273"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1078599"},{"key":"e_1_2_6_12_2","first-page":"57","volume":"7","author":"Waller R. 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