Simultaneous Profiling of Palmitoylomics and Glycomics with Photo/pH Dual‐Responsive Magnetic Nanocomposites

Abstract Following an in‐depth examination of a single type of protein posttranslational modification, the synergistic analysis of two or more modification types has gradually emerged as a focal point in proteomic research. Palmitoylation and glycosylation are both critical for protein, implicated in carcinogenesis and inflammation. In this study, novel dual‐responsive magnetic nanocomposites that serve as an ideal platform for the sequential or simultaneous enrichment of palmitoyl and glycopeptides are reported. The nanocomposites denoted as magDVS‐VBA are constructed by modifying magnetic nanoparticles with azobenzene and divinyl sulfone (DVS), and self‐assembled with 4‐vinylbenzeneboronic acid (VBA)‐immobilized β ‐cyclodextrin, which responds to light. The incorporated DVS component possesses the ability to recognize palmitoyl or glycopeptides under different pH conditions, whereas the introduction of VBA enhances the affinity of the nanocomposite for glycopeptides. Notably, magDVS‐VBA exhibits flexible photo‐, pH‐, and magnetic‐responsive capabilities, enabling the simultaneous recognition of hydrophobic palmitoyl peptides and hydrophilic glycopeptides for the first time. The developed platform demonstrates high specificity for sensitive palmitoylomics and glycomics analysis of mouse liver tissue, providing an effective method for studying of their crosstalk, and potential implications in clinical applications.