Probing Sialidases or Siglecs with Sialic Acid Analogues, Clusters and Precursors

Sialic acids have recently gathered interests of many researchers. Sialidases and Siglecs are two important sialic acids‐related proteins that exist in biological systems, and aberrant sialoside‐Siglec or sialoside‐sialidase interactions are associated with many diseases, including autoimmunity, infection and cancer. Probing sialidase and Siglec effectively can enable the studies on the complex physiological functions of sialic acids. Over the last few decades, many sialic acid derivatives with modifications of parent skeleton and aglycon have been designed to increase the binding affinity with sialidase/Siglec or improve their detection efficiency. At the same time, in‐situ detection has also been aided by metabolic oligosaccharide engineering, in which incubating cells with sialic acid precursors could result in unnatural sialylated glycans incorporated into cellular membrane. In this minireview, we will predominantly highlight the development of sialidase and Siglec probing strategies using sialic acid analogues, clusters and precursors, which may further lay foundation for new diagnostics and treatments.