Construction of magnetic MOF@COF hybrid via covalent integration for simultaneous identification of glyco‑ and phospho-proteins in human urine

Abstract

Urine plays a great role in reflecting the physiological and pathological conditions of kidney. Glyco- and phospho-proteins in urine are important indicator for diagnosing kidney diseases biomarkers, while their low concentration and extremely complex composition in urine samples make it difficult for direct analysis. Pretreatment of urine samples including acetone extraction or ultrafiltration concentration are often required before the enrichment procedure and subsequent analysis step. Herein, we developed a novel strategy to achieve “mega mergers” via covalent integration of two promising porous crystal materials (MOF@COF) on the magnetic core. The Ti-O groups in the MOF and high hydrophilicity of COF endow the resulting porous hybrid with high-efficiency simultaneous enrichment capacity of glyco- and phospho-proteins from urine samples without additional pretreatment steps. The enrichment mechanism and possible binding modes were validated by theoretical calculations. The synthesized magnetic MOF@COF successfully enriched glyco- and phospho-proteins from urine samples of patients with nephrotic syndrome and healthy controls, indicating that the protocol can be used to distinguish patients with nephrotic syndrome based on the amount of enriched glycoproteins and phosphoproteins. This work not only provides a new idea for the efficient enrichment of glyco- and phospho-proteins with porous hybrid material, but also broadens the research possibilities for biomarker discovery in urine-based liquid biopsy.