| Download | - View accepted manuscript: Synthesis and evaluation of L-Rhamnose 1C-Phosphonates as nucleotidylyltransferase inhibitors (PDF, 1.3 MiB)
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| DOI | Resolve DOI: https://doi.org/10.1021/jo401542s |
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| Author | Search for: Loranger, Matthew W.; Search for: Forget, Stephanie M.; Search for: Mccormick, Nicole E.; Search for: Syvitski, Raymond T.1; Search for: Jakeman, David L. |
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| Affiliation | - National Research Council of Canada. Aquatic and Crop Resource Development
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| Format | Text, Article |
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| Abstract | 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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| Publication date | 2013-09-10 |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| NRC number | NRCC 55823 |
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| NPARC number | 21268658 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | d9f6c1ac-fb26-44cf-a378-3c1d2f186d05 |
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| Record created | 2013-11-06 |
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| Record modified | 2020-06-04 |
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