Facile synthesis of layered mesoporous covalent organic polymers for highly selective enrichment of N-glycopeptides

Hydrophilic interaction liquid chromatography is a significant strategy for the separation and enrichment of glycoproteins and glycopeptides. A layered imine-based covalent organic polymer with mesopores (denoted as p-TpBDH) was successfully fabricated by a facile solvothermal method. Then p-TpBDH-OH with abundant hydrophilic groups was evolved from p-TpBDH by the direct reduction. 36 and 40 glycopeptides were identified from IgG digests respectively by p-TpBDH and p-TpBDH-OH. Furthermore, the p-TpBDH-OH exhibits superior selectivity (IgG: BSA = 1: 250) for glycopeptides compared with the p-TpBDH. Encouragingly, a total of 463 glycopeptides assigned to 173 glycoproteins were finally identified from only 2 μL human serum by the p-TpBDH-OH. Compared with p-TpBDH, abundant hydrophilic and nitrogen-containing affinity sites of p-TpBDH-OH facilitate effective hydrophilic interaction between the polymeric material and glycopeptides. All the results demonstrate the functionalized hydrophilic covalent organic polymer has great potential in large-scale N-glycoproteomic research. [Display omitted] •The layered covalent organic polymer p-TpBDH-OH with mesopores was fabricated by a facile reduction of p-TpBDH.•TpBDH-OH exhibit excellent performance and high selectivity for capturing glycopeptides from complicated biosamples due to its enhanced hydrophilicity and specific porous structure.