What Is Hidden Behind Schiff Base Hydrolysis? Dynamic Covalent Chemistry for the Precise Capture of Sialylated Glycans

Abstract

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, the identification and comprehensive analysis of SGs are exceptionally complex, which urgently need an innovative and effective method of capturing SGs from biosamples prior to MS analysis. Here, we report that a novel dynamic covalent chemistry strategy based on Schiff base hydrolysis can be applied to the precise capture of SGs. The prepared glucopyranoside−Schiff base-modified silica gel displays extraordinary enrichment selectivity (even at a ratio of 1:5000 with interference), high adsorption capacity (120 mg•g −1 ), and satisfying enrichment recovery (95.5%) toward sialylated glycopeptides, contributing 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.

Genotoxic C8-Arylamino-2′-deoxyadenosines Act as Latent Alkylating Agents to Induce DNA Interstrand Cross-Links

“…Imine formation is a reversible process and is the likely source of piperidine sensitivity for these ArNHdA oxidation reactions (Figures and ). The presence of adenine iminopurine can cause cross-link formation to be reversible to varying degrees . We posit that this imine is likely stabilized through resonance in the case of all ArNHdA lesions.…”

“…The presence of adenine iminopurine can cause cross-link formation to be reversible to varying degrees. 107 We posit that this imine is likely stabilized through resonance in the case of all ArNHdA lesions. However, the degree to which the prerequisite diiminoadenine and final cross-linked structures are stabilized will vary based on the character of the C8 adduct, which could give rise to the reactivity trends seen in Figures 3 and 5.…”

Highly Efficient Separation of Methylated Peptides Utilizing Selective Complexation between Lysine and 18-Crown-6

“…Binding Affinity Analysis. Then, nuclear magnetic resonance (NMR) titration experiments 29 were performed to investigate the interaction between 18-crown-6 and a 15 Nlabeled lysine methyl ester hydrochloride, the chemical structure of which is shown in the inset of Figure 3C. Carbonyl acid of lysine was protected by methyl ester (Scheme S1) to eliminate its influence, and both αand β-NH 2 were protonated in accordance with the acidic separation condition (Figure 2F).…”

A Pragmatic Guide to Enrichment Strategies for Mass Spectrometry–Based Glycoproteomics

“…We anticipate that boronic acid–based enrichments will gain popularity as novel materials continue to improve the strength of boronic acid–glycan interactions and continue to become more available. Furthermore, continued development of reversible covalent modifications, such as a recently described Schiff base hydrolysis strategy ( 353 ), will continue to enable intact glycopeptide enrichment. Also of interest are host–guest interactions, which can enable reversible capture of glycosylated species with specificities for monosaccharides, e.g.…”