What is hidden behind Schiff base hydrolysis? Dynamic covalent chemistry for precise capture of sialylated glycans.

The aberrant expression of sialylated glycans (SGs) is closely associated with the occurrence, progression, and metastasis of various cancers, and sialylated glycoproteins have been widely used as clinical biomarkers for cancers. However, identification and comprehensive analysis of SGs is exceptionally complex, which urgently need innovative and effective method to capture SGs from biosample in prior to MS analysis. Here, we report that a novel dynamic covalent chemistry strategy based on Schiff base hydrolysis can be applied for the precise capture of the SGs. The prepared Glucopyranoside-Schiff base-modified silica gel displays extraordinary enrichment selectivity (even at the ratio of 1:5000 with interference), high adsorption capacity (120 mg*g(-1)), and satisfying enrichment recovery (95.5 %) towards sialylated glycopeptides, which contributes to a highly specific, efficient, mild and reversible SG capturing approach that can remarkably promote the development of glycoproteomics and sialic acid sensing devices, and can be considerably promising in cancer biomarker discovery. Meanwhile, the facile hydrolysis characteristic of our Schiff base material completely subverts conventional knowledge of enrichment materials, the chemical stability of which is usually regarded as a prerequisite. Importantly, we find an exciting story hidden behind the Schiff base hydrolysis reaction, which demonstrates the unique advantage of dynamic covalent chemistry in glycoproteomics and biomolecule sensing.