Azide-Functionalized Derivatives of the Virulence-Associated Sugar Pseudaminic Acid: Chiral Pool Synthesis and Labeling of Bacteria.
Amol M VibhuteHideki TamaiDana LogviniukPeter G JonesMicha FridmanDaniel B WerzPublished in: Chemistry (Weinheim an der Bergstrasse, Germany) (2021)
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.
Keyphrases
- gram negative
- multidrug resistant
- escherichia coli
- pseudomonas aeruginosa
- staphylococcus aureus
- cell surface
- induced apoptosis
- biofilm formation
- quantum dots
- antimicrobial resistance
- cell cycle arrest
- type diabetes
- cell death
- molecularly imprinted
- metabolic syndrome
- cystic fibrosis
- insulin resistance
- adipose tissue
- endoplasmic reticulum stress
- capillary electrophoresis
- blood pressure
- ionic liquid
- weight loss
- blood glucose
- pi k akt