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Proteomics is a widely used approach to study host\u2010pathogen systems and to identify drug protein targets. Plasmodione is an antiplasmodial early\u2010lead drug exerting potent activities against young asexual and sexual blood stages in\u2005vitro with low toxicity to host cells. To elucidate its molecular mechanisms, an affinity\u2010based protein profiling (AfBPP) approach was applied to yeast and <jats:italic>P. falciparum<\/jats:italic> proteomes. New (<jats:italic>pro\u2010<\/jats:italic>) AfBPP probes based on the 3\u2010benz(o)yl\u20106\u2010fluoro\u2010menadione scaffold were synthesized. With optimized conditions of both photoaffinity labeling and click reaction steps, the AfBPP protocol was then applied to a yeast proteome, yielding 11 putative drug\u2010protein targets. Among these, we found four proteins associated with oxidoreductase activities, the hypothesized type of targets for plasmodione and its metabolites, and other proteins associated with the mitochondria. In <jats:italic>Plasmodium<\/jats:italic> parasites, the MS analysis revealed 44 potential plasmodione targets that need to be validated in further studies. Finally, the localization of a 3\u2010benzyl\u20106\u2010fluoromenadione AfBPP probe was studied in the subcellular structures of the parasite at the trophozoite stage.<\/jats:p>","DOI":"10.1002\/cbic.202400187","type":"journal-article","created":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T06:15:05Z","timestamp":1713507305000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Proteomic Profiling of Antimalarial Plasmodione Using 3\u2010Benz(o)ylmenadione Affinity\u2010Based Probes"],"prefix":"10.1002","volume":"25","author":[{"given":"Ilaria","family":"Iacobucci","sequence":"first","affiliation":[{"name":"Laboratoire d'Innovation Mol\u00e9culaire et Applications (LIMA) Team Bio(IN)organic &amp; Medicinal Chemistry UMR7042 CNRS-Universit\u00e9 de Strasbourg-Universit\u00e9 Haute-Alsace European School of Chemistry Polymers and Materials (ECPM), 25  rue Becquerel, 25, rue Becquerel F-67087 Strasbourg France"},{"name":"Laboratoire de Spectrom\u00e9trie de Masse BioOrganique IPHC UMR 7178 CNRS Universit\u00e9 de Strasbourg  67087 Strasbourg France"},{"name":"Infrastructure Nationale de Prot\u00e9omique ProFI \u2013 FR2048  F-67087 Strasbourg France"},{"name":"Department of Chemical Sciences University of Naples Federico II Complesso Universitario di Monte Sant' Angelo  Via Cintia 26 I-80126 Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittoria","family":"Monaco","sequence":"additional","affiliation":[{"name":"Laboratoire d'Innovation Mol\u00e9culaire et Applications (LIMA) Team Bio(IN)organic &amp; Medicinal Chemistry UMR7042 CNRS-Universit\u00e9 de Strasbourg-Universit\u00e9 Haute-Alsace European School of Chemistry Polymers and Materials (ECPM), 25  rue Becquerel, 25, rue Becquerel F-67087 Strasbourg France"},{"name":"Laboratoire de Spectrom\u00e9trie de Masse BioOrganique IPHC UMR 7178 CNRS Universit\u00e9 de Strasbourg  67087 Strasbourg France"},{"name":"Infrastructure Nationale de Prot\u00e9omique ProFI \u2013 FR2048  F-67087 Strasbourg France"},{"name":"Department of Chemical Sciences University of Naples Federico II Complesso Universitario di Monte Sant' Angelo  Via Cintia 26 I-80126 Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Hovasse","sequence":"additional","affiliation":[{"name":"Laboratoire de Spectrom\u00e9trie de Masse BioOrganique IPHC UMR 7178 CNRS Universit\u00e9 de Strasbourg  67087 Strasbourg France"},{"name":"Infrastructure Nationale de Prot\u00e9omique ProFI \u2013 FR2048  F-67087 Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baptiste","family":"Dupouy","sequence":"additional","affiliation":[{"name":"Laboratoire d'Innovation Mol\u00e9culaire et Applications (LIMA) Team Bio(IN)organic &amp; Medicinal Chemistry UMR7042 CNRS-Universit\u00e9 de Strasbourg-Universit\u00e9 Haute-Alsace European School of Chemistry Polymers and Materials (ECPM), 25  rue Becquerel, 25, rue Becquerel F-67087 Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigue","family":"Keumoe","sequence":"additional","affiliation":[{"name":"Institut de Biologie Mol\u00e9culaire et Cellulaire INSERM U1257 \u2013 CNRS UPR9022 \u2013 Universit\u00e9 de Strasbourg  2, All\u00e9e Konrad Roentgen -67084 Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan","family":"Cichocki","sequence":"additional","affiliation":[{"name":"Laboratoire d'Innovation Mol\u00e9culaire et Applications (LIMA) Team Bio(IN)organic &amp; Medicinal Chemistry UMR7042 CNRS-Universit\u00e9 de Strasbourg-Universit\u00e9 Haute-Alsace European School of Chemistry Polymers and Materials (ECPM), 25  rue Becquerel, 25, rue Becquerel F-67087 Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mourad","family":"Elhabiri","sequence":"additional","affiliation":[{"name":"Laboratoire d'Innovation Mol\u00e9culaire et Applications (LIMA) Team Bio(IN)organic &amp; Medicinal Chemistry UMR7042 CNRS-Universit\u00e9 de Strasbourg-Universit\u00e9 Haute-Alsace European School of Chemistry Polymers and Materials (ECPM), 25  rue Becquerel, 25, rue Becquerel F-67087 Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Meunier","sequence":"additional","affiliation":[{"name":"Institute for Integrative Biology of the Cell (I2BC) CEA CNRS  Univ. 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