Azide-Functionalized Derivatives of the Virulence-Associated Sugar Pseudaminic Acid: Chiral Pool Synthesis and Labeling of Bacteria |
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Authors: | Dr Amol M Vibhute Dr Hideki Tamai Dana Logviniuk Prof Dr Peter G Jones Prof Dr Micha Fridman Prof Dr Daniel B Werz |
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Institution: | 1. Technische Universität Braunschweig, Institute of Organic Chemistry, Hagenring 30, 38106 Braunschweig, Germany;2. School of Chemistry, Raymond and Beverley Sackler Faculty of Exact Sciences, Tel Aviv University, 6997801 Tel Aviv, Israel;3. Technische Universität Braunschweig, Institute of Inorganic and Analytical Chemistry, Hagenring 30, 38106 Braunschweig, Germany |
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Abstract: | Pseudaminic acid (Pse) is a significant prokaryotic monosaccharide found in important Gram-negative and Gram-positive bacteria. This unique sugar serves as a component of cell-surface-associated glycans or glycoproteins and is associated with their virulence. We report the synthesis of azidoacetamido-functionalized Pse derivatives as part of a search for Pse-derived metabolic labeling reagents. The synthesis was initiated with d -glucose (Glc), which served as a cost-effective chiral pool starting material. Key synthetic steps involve the conversion of C1 of Glc into the terminal methyl group of Pse, and inverting deoxyaminations at C3 and C5 of Glc followed by backbone elongation with a three-carbon unit using the Barbier reaction. Metabolic labeling experiments revealed that, of the four Pse derivatives, ester-protected C5 azidoacetamido-Pse successfully labeled cells of Pse-expressing Gram-positive and Gram-negative strains. No labeling was observed in cells of non-Pse-expressing strains. The ester-protected and C5 azidoacetamido-functionalized Pse is thus a useful reagent for the identification of bacteria expressing this unique virulence-associated nonulosonic acid. |
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Keywords: | azidoacetamide bacteria chiral pool metabolic labeling pseudaminic acid |
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