Bacterial glycans are compelling therapeutic targets that can be harnessed to develop novel antibiotics, as they contain unusual monosaccharides linked to pathogenesis that are absent from human cells. However, the systematic study of bacterial glycans remains challenging due to the presence of exclusively bacterial sugars, including rare deoxy amino L-sugars, which hamper traditional glycan analyses. Thus, the development of chemical tools to study bacterial glycans is a crucial step toward understanding and altering these biomolecules. Here, we used a metabolic glycan labeling-based approach to accelerate the investigation of bacterial glycans bearing distinctive L-monosaccharides. Briefly, we developed azide-containing analogs of N-acetyl L-fucosamine, N-acetyl L-pneumosamine, N-acetyl-L-quinovosamine, and N-acetyl L-rhamnosamine and explored their metabolic incorporation into glycans in a range of Gram-negative bacteria. L-sugar analogs were narrowly incorporated into discrete glycans in select bacteria, consistent with the rare distribution of these epitopes. Further application of these rare sugar-based probes will refine our knowledge of glycans in diverse bacteria and aid the design of novel antibiotics.

Development of rare deoxy amino L-sugar analogs to probe glycans in pathogenic bacteria

ACS Spring 2022

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