| Téléchargement | - Voir le manuscrit accepté : Synthesis and evaluation of L-Rhamnose 1C-Phosphonates as nucleotidylyltransferase inhibitors (PDF, 1.3 Mio)
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| DOI | Trouver le DOI : https://doi.org/10.1021/jo401542s |
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| Auteur | Rechercher : Loranger, Matthew W.; Rechercher : Forget, Stephanie M.; Rechercher : Mccormick, Nicole E.; Rechercher : Syvitski, Raymond T.1; Rechercher : Jakeman, David L. |
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| Affiliation | - Conseil national de recherches du Canada. Développement des cultures et des ressources aquatiques
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| Format | Texte, Article |
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| Résumé | We report the synthesis of a series of phosphonates and ketosephosphonates possessing an l-rhamnose scaffold with varying degrees of fluorination. These compounds were evaluated as potential inhibitors of α-d-glucose 1-phosphate thymidylyltransferase (Cps2L), the first enzyme in Streptococcus pneumoniae l-rhamnose biosynthesis, and a novel antibiotic target. Enzyme–substrate and enzyme–inhibitor binding experiments were performed using water-ligand observed binding via gradient spectroscopy (WaterLOGSY) NMR for known sugar nucleotide substrates and selected phosphonate analogues. IC50 values were measured and Ki values were calculated for inhibitors. New insights were gained into the binding promiscuity of enzymes within the prokaryotic l-rhamnose biosynthetic pathway (Cps2L, RmlB–D) and into the mechanism of inhibition for the most potent inhibitor in the series, l-rhamnose 1C-phosphonate. |
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| Date de publication | 2013-09-10 |
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| Dans | |
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| Langue | anglais |
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| Publications évaluées par des pairs | Oui |
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| Numéro du CNRC | NRCC 55823 |
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| Numéro NPARC | 21268658 |
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| Exporter la notice | Exporter en format RIS |
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| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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| Identificateur de l’enregistrement | d9f6c1ac-fb26-44cf-a378-3c1d2f186d05 |
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| Enregistrement créé | 2013-11-06 |
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| Enregistrement modifié | 2020-06-04 |
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