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.