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

ABSTRACT 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 Fe 3 O 4 , was sequentially coated with SiO 2 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 Fe 3 O 4 @SiO 2 @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.