Dipeptide-Based Carbohydrate Receptors and Polymers for Glycopeptide Enrichment and Glycan Discrimination

Glycoproteomics identifies and catalogs protein glycosylation and explores its impact on protein conformations and biofunctions. However, these studies are restricted by the bottleneck to enrich low-abundance glycopeptides from complex biosamples and the difficulties in analyzing glycan structures by mass spectrometry. Here, we report dipeptide as a simple but promising carbohydrate binding platform to tackle these problems. We build a hydropathy-index-based strategy for sequence optimization and screen out three optimal dipeptide sequences from 54 types of dipeptides. The optimized dipeptide-based homopolymers display excellent performance (e.g., selectivity up to ∼70% for real biosamples and strong anti-interference capacity capable of resisting 1000-fold bovine serum albumin interference) in glycopeptide enrichment. Meanwhile, our polymers exhibit high-efficiency chromatographic separation toward oligosaccharides with different compositions, polymerization degrees and even their linkage isomers. This brings another attractive feature that our materials can discriminate subtly variable glycan structures of glycopeptides, especially, isomeric glycosidic linkages. These features provide a solid foundation to analyze the complex glycan structures and glycosites simultaneously, which will benefit future development of glycoproteomics and glycobiology.