Enrichment driven glycoproteomics: New materials, new methods, and beyond

Glycoproteomics is a rapidly growing field that aims to identify and characterize protein glycosylation events at a system level. However, the analysis of protein glycosylation in complex samples is still challenging due to several factors: the low amounts of glycopeptides produced after glycoprotein digestion, the suppression of the glycopeptide mass spectrometry signals in the presence of peptides, and the high heterogeneity of glycopeptides. Therefore, efficient enrichment of glycopeptides from complex samples is crucial. Nowadays, a continuous effort has been made to improve glycopeptide enrichment through the design of substrates and functional moieties of materials, which have proven to be immensely valuable in glycopeptide analysis. In-depth glycoproteomic analysis will further help to better understand glycoprotein functions and the molecular mechanisms of diseases. This review summarizes novel glycopeptide enrichment materials and approaches, and discusses the application of glycoproteomics in both the functional analysis of glycoproteins and the study of human diseases.