A Clickable Bioorthogonal Sydnone‐Aglycone for the Facile Preparation of a Core 1 O‐Glycan‐Array

Protein‐O‐glycosylation has been shown to be essential for many biological processes. However, determining the exact relationship between O‐glycan structures and their biological activity remains challenging. Here we report that, unlike azides, sydnones can be incorporated as an aglycon into core 1 O‐glycans early‐on in their synthesis since it is compatible with carbohydrate chemistry and enzymatic glycosylations, allowing us to generate a small library of sydnone‐containing core 1 O‐glycans by chemoenzymatic synthesis. The sydnone‐aglycon was then employed for the facile preparation of an O‐glycan array, via bioorthogonal strain‐promoted sydnone‐alkyne cycloaddition click reaction, and in turn was utilized for the high‐throughput screening of O‐glycan‐lectin interactions. This sydnone‐aglycon, particularly adapted for O‐glycomics, is a valuable chemical tool that complements the limited technologies available for investigating O‐glycan structure‐activity relationships.