Construction of a hydrophilic porphyrin-based MOF@COF hybrid via post-synthetic modification for N-glycopeptides analysis in human serum

Abstract

A hybrid material, M@C-Br@GMA@Glu, consisting of a porphyrin-based metal–organic framework-covalent organic framework (MOF@COF), has been meticulously synthesized using a post-synthetic modification approach. This advanced material has demonstrated exceptional effectiveness in glycopeptide enrichment, characterized by an impressively low detection limit (0.2 fmol μL⁻¹), high selectivity (1 : 2000), and loading capacity for glycopeptides (100 mg g⁻¹). In practical applications with complex biological samples, 210 glycopeptides associated with 87 glycoproteins from the serum of the healthy group, and 156 glycopeptides related to 85 glycoproteins from the serum of cervical cancer were identified after enrichment with M@C-Br@GMA@Glu. Subsequent genetic ontology analysis has elucidated the relationship between cervical cancer and glycosylation, focusing on biological processes such as complement activation, innate immune response mechanisms, and the structural dynamics of the extracellular matrix. The collective findings not only validate the material's proficiency in the sensitive and selective enrichment of glycopeptides, but also underscore its potential in biomarker discovery applications.