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- Alejandro Mahía
- Department of Chemistry Aarhus University Langelandsgade 140 8000 Aarhus C Denmark
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- Anders E. Kiib
- Department of Chemistry Aarhus University Langelandsgade 140 8000 Aarhus C Denmark
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- Marija Nisavic
- Department of Chemistry Aarhus University Langelandsgade 140 8000 Aarhus C Denmark
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- Esben B. Svenningsen
- Department of Chemistry Aarhus University Langelandsgade 140 8000 Aarhus C Denmark
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- Johan Palmfeldt
- Department of Clinical Medicine—Research Unit for Molecular Medicine Aarhus University Hospital Palle Juul-Jensens Boulevard 82 8200 Aarhus N Denmark
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- Thomas B. Poulsen
- Department of Chemistry Aarhus University Langelandsgade 140 8000 Aarhus C Denmark
説明
<jats:title>Abstract</jats:title><jats:p>Electrophilic groups are one of the key pillars of contemporary chemical biology and medicinal chemistry. For instance, 3‐membered <jats:italic>N</jats:italic>‐heterocyclic compounds—such as aziridines, azirines, and oxaziridines—possess unique electronic and structural properties which underlie their potential and applicability as covalent tools. The α‐lactams are also members of this group of compounds, however, their utility within the field remains unexplored. Here, we demonstrate an α‐lactam reagent (<jats:bold>AM2</jats:bold>) that is tolerant to aqueous buffers while being reactive towards biologically relevant nucleophiles. Interestingly, carboxylesterases 1 and 2 (CES1/2), both serine hydrolases with key roles in endo‐ and xenobiotic metabolism, were found as primary covalent targets for <jats:bold>AM2</jats:bold> in HepG2 liver cancer cells. All in all, this study constitutes the starting point for the further development and exploration of α‐lactam‐based electrophilic probes in covalent chemical biology.</jats:p>
収録刊行物
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- Angewandte Chemie International Edition
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Angewandte Chemie International Edition 62 (26), 2023-05-15
Wiley