We describe a simple method for efficiently labeling cell-surface sialic acid–containing
glycans on living animal cells. The method uses mild periodate oxidation to generate an
aldehyde on sialic acids, followed by aniline-catalyzed oxime ligation with a suitable tag.
Aniline catalysis dramatically accelerates oxime ligation, allowing use of low concentrations
of aminooxy-biotin at neutral pH to label the majority of cell-surface sialylated glycoproteins
while maintaining high cell viability.