Synthesis and Validation of Dextran-Based Hydrophilic Magnetic Nanomaterials for Glycopeptide Enrichment

Glycopeptide enrichment is an essential prerequisite in mass spectrometry (MS)-based protein glycosylation studies, due to the low abundance of glycosylated peptides and the high complexity of biological samples, which contain substantial interference from non-glycosylated metabolites. Current enrichment strategies commonly exploit the polar interactions between glycans and hydrophilic solid-phase materials. Building on existing magnetic-core particles, we developed a series of novel magnetic materials with surfaces functionalized with dextran and amide groups. The magnetic core, composed of polyvinylpyrrolidone (PVP) and Fe₃O₄, was sequentially coated with SiO₂ and dextran. Amide groups were then conjugated to the dextran layer via a condensation reaction between carboxy-modified dextran and ethanolamine. The glycopeptide enrichment performance of five resulting magnetic materials was evaluated using IgG and rat serum samples. One material, designated Fe₃O₄@SiO₂@Dextran-Amide (Dextran-polyamide-717), demonstrated superior sensitivity for glycopeptide detection and strong resistance to nonspecific interference. Moreover, Dextran-polyamide-717 exhibited higher enrichment efficiency in both IgG and serum samples compared to two commercially available products. With its multilayer surface modification strategy, Dextran-polyamide-717 shows great promise for advanced applications in glycoproteomic research.