Fabrication of magnetic dual-hydrophilic metal organic framework for highly efficient glycopeptide enrichment

Highly selective glycopeptide enrichment is important before mass spectrometry analysis because of the ultra-low abundance of glycopeptides in the peptide mixtures. Herein, a UiO-66-NH₂-based magnetic composite was prepared and used for the hydrophilic enrichment of glycopeptides. The composite was modified with phytic acid (PA) molecules by partially replacing 2-aminoterephthalic acid ligands in UiO-66-NH₂, with electrostatic interactions also promoting this modification process. Based on the hydrophilicity of both the PA molecules and the UiO-66-NH₂ skeleton, the resulting material, denoted as MUiO-66-NH₂/PA, showed excellent dual hydrophilicity towards glycopeptide enrichment. Compared with pure UiO-66-NH₂, the specific surface area and hydrophilicity of the prepared material were increased, and MUiO-66-NH₂/PA exhibited good magnetic responsiveness to facilitate a convenient enrichment procedure. HRP and IgG were used as standard proteins to evaluate the glycopeptide enrichment properties, with 21 and 34 glycopeptides enriched from their tryptic digests. Furthermore, MUiO-66-NH₂/PA showed outstanding sensitivity (1 fmol/μL) and selectivity (HRP/BSA = 1:1000), and achieved remarkable glycopeptide enrichment performance for practical human serum samples. Notably, MUiO-66-NH₂/PA showed perfect reusability and stability, achieving enrichment performance after five cycles similar to that of the first use. This material can be used for glycopeptide enrichment to obtain further glycosylation information, providing the possibility for cancer treatment.