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The discovery of protein modifiers may be initiated by screens of diverse sets of reactive fragments. A modular synthesis of diverse pentafluorobenzenesulfonamide reactive fragments was developed, which was based on the reaction between diverse, readily\u2010available substrates and rhodium nitrenoid intermediates formed from pentafluorobenzenesulfonamide. The approach enabled the synthesis of 21 reactive fragments whose diversity stemmed from both that of the substrates and the rich chemistry of rhodium nitrenoids. The fragments were found to modify Aurora A kinase via several distinct pathways. Furthermore, five of the reactive fragments were profiled against HeLa cell lysate, which demonstrated that the constellation of modified cysteines was critically dependent on the specific reactive fragment used. Overall, the modular Rh\u2010catalyzed connective approach enabled the synthesis of reactive fragments with high structural and reactivity diversity. We envisage that such reactive fragments may provide useful starting points for the discovery of covalent modifiers of proteins, including chemical probes and drugs.<\/jats:p>","DOI":"10.1002\/chem.202600009","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:06:16Z","timestamp":1775804776000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modular Rh\u2010Catalyzed Synthesis and Biological Profiling of Diverse Pentafluorobenzenesulfonamide Reactive Fragments"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5416-7648","authenticated-orcid":false,"given":"Julian","family":"Chesti","sequence":"first","affiliation":[{"name":"School of Chemistry University of Leeds  Leeds UK"},{"name":"Astbury Centre for Structural Molecular Biology University of Leeds  Leeds 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