Nanostructure stable hydrophilic hierarchical porous metal-organic frameworks for highly efficient enrichment of glycopeptides.

Protein glycosylation plays a vital role in many physiological activities in organisms. Due to the low abundance of glycopeptides and the interference of numerous non-glycopeptides in biological samples, selective enrichment of glycopeptides is of great significance for their successful identification. Metal organic frameworks (MOFs) materials are appropriate for glycopeptides enrichment by virtue of their large specific surface area and outstanding hydrophilic properties. However, the instability of hydrophilic MOFs in acidic solutions have severely limited their applications. In this work, a rational facile strategy was established to synthesize a stable hydrophilic hierarchical porous MOF (denoted as HP-MOF-Arg@mSiO 2). This new material improved the selectivity and sensitivity of enrichment for glycopeptides via modification of arginine groups. More importantly, the mesoporous silica layer was introduced to enhance the stability of MOFs in aqueous solution and achieve the size exclusion effect of large-size proteins in complex samples. Overall, owing to the unique hierarchical porous and the hydrophilic modification, the synthesized HP-MOF-Arg@mSiO 2 materials showed excellent hydrophilicity and hydrolytic stability, resulting in outstanding specific separation capacity in glycopeptides enrichment. A total of 521 and 342 glycopeptides were respectively captured from 2 μL human serum digests and mouse testis tissue digests, revealing the potential of the materials in the study of glycoproteomics in complex biological samples. [Display omitted] • A novel stable hydrophilic hierarchical porous MOFs was designed for glycopeptide enrichment. • The hydrophilicity and hydrolytic stability of MOFs in acidic solutions were greatly improved. • MOFs materials showed outstanding enrichment specificity and sensitivity. • MOFs materials were applied to the detection of glycopeptides from biosamples by nano-LC-MS/MS. [ABSTRACT FROM AUTHOR]