Sialic Acid Derivatives Inhibit SiaT Transporters and Delay Bacterial Growth
| Autor: | Tiago Bozzola, Mariafrancesca Scalise, Christer U. Larsson, Michael C. Newton-Vesty, Caterina Rovegno, Ankita Mitra, Jonathan Cramer, Weixiao Yuan Wahlgren, Partha Radhakrishnan Santhakumari, Richard E. Johnsson, Oliver Schwardt, Beat Ernst, Rosmarie Friemann, Renwick C. J. Dobson, Cesare Indiveri, Jenny Schelin, Ulf J. Nilsson, Ulf Ellervik |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | ACS Chemical Biology. 17:1890-1900 |
| ISSN: | 1554-8937 1554-8929 |
| Popis: | Antibiotic resistance is a major worldwide concern, and new drugs with mechanistically novel modes of action are urgently needed. Here, we report the structure-based drug design, synthesis, and evaluation in vitro and in cellular systems of sialic acid derivatives able to inhibit the bacterial sialic acid symporter SiaT. We designed and synthesized 21 sialic acid derivatives and screened their affinity for SiaT by a thermal shift assay and elucidated the inhibitory mechanism through binding thermodynamics, computational methods, and inhibitory kinetic studies. The most potent compounds, which have a 180-fold higher affinity compared to the natural substrate, were tested in bacterial growth assays and indicate bacterial growth delay in methicillin-resistant |
| Databáze: | OpenAIRE |
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