Food-derived glycopeptides: structural insights, glycosylation-driven bioactivity, and translational potential in health and functional applications

Background: Bioactive peptides are susceptible to degradation during gastrointestinal (GI) digestion, which may alter their bioactivity depending on their structural characteristics. In contrast, glycopeptides (GPs) exhibit superior stability and bioactivity owing to the presence of glycan chains. Food-derived GPs demonstrate broad application prospects due to their diverse natural sources (including animals, plants, and microorganisms) and multifunctional bioactivities. Scope and approach: This review discusses the sources, bioactivities, and potential structure-activity relationships of GPs, emphasizing the role of glycan chains in their structure, properties, and GI digestion and absorption characteristics. It summarizes methods for GP extraction, preparation, purification, enrichment, and structural identification, and explores their application prospects. Finally, it identifies research deficiencies in structureactivity relationships, clinical translation, and large-scale production, and proposes future research directions. Key findings and conclusions: Glycans endow GPs with enhanced bioactivity and stability by strengthening the spatial conformation of the peptide chain. Compared to non-glycosylated peptides, GPs exhibit superior GI digestion and absorption characteristics. Bioactive GPs can be obtained through methods such as enzymatic hydrolysis, microbial fermentation, and glycosylation reactions. Advanced purification techniques significantly enhance the purity of GPs. Mass spectrometry-based omics analysis platforms and bioinformatics enable precise analysis and prediction of GP structure and properties. Recently, significant advancements in artificial intelligence and machine learning have greatly impacted GP research. These methods represent the forefront of GP research, driving innovation and shaping future directions in the field. This review provides forward-thinking insights into the innovative applications of Food-derived GPs across various fields.