Decoding glycan protein interactions by a new class of asymmetric N-glycans

Abstract

N -glycans are normally involved in crucial physiological and disease processes by interactions with glycan binding proteins. So far structurally defined N-glycans are good candidates for glycan binding study. Herein, a class of homogeneous asymmetric N-glycans was synthesized by coupling glycan-oxazoline and N-glycans using EndoM N175Q catalyzed quick glycan extension. Branch-biased binding and spacial inhibition caused by bulky group on the other branch of N-glycan were observed in glycan protein interactions involving lectins and these glycans by glycan microarray study. These new compounds are valuable for functional glycomic studies to better understand new functions of glycans and glycan-binding proteins.

Deciphering Protein Glycosylation by Computational Integration of On-chip Profiling, Glycan-array Data, and Mass Spectrometry

“…Bead-based arrays may be particularly useful for rapid customization (39). In addition, new synthetic methods are enabling the production of structures that were previously difficult to synthesize, such as asymmetrically branched N-glycans (40, 41), which could reveal unusual fine specificities in lectins or glycosidases (16). Integrating glycan-array analyses with lectin structural information (42) also promises to increase precision in charactering specificities.…”

Combined Analysis of Multiple Glycan-Array Datasets: New Explorations of Protein–Glycan Interactions

“…Fortunately, new synthesis strategies have resulted in the production of an increasing diversity of higher-complexity structures. The new structures include various types of sialylated structures, − human milk oligosaccharides, and asymmetrically branched N -glycans. , In addition, microarrays have been developed to cover additional classes of glycans, including arrays of microbial glycans, plant cell–wall glycans, and fully-defined heparan sulfate glycans . New experimental systems for glycan presentation and detection include a glycan bead array, a next-generation glycan microarray (NGGM), and a competitive universal proxy receptor assay (CUPRA) .…”

Recent Advances in the Chemical Biology of N-Glycans

“…Meanwhile, recent advances in the preparation of the whole structure of various N -glycans have allowed the full realization of structure–activity relationships, elucidating the significance of complexity of N -glycan structures ( Figure 4 ). For example, these advances have provided insights into the differences in the lectin recognition of each branch [ 49 , 50 , 51 , 52 , 53 , 54 ], the improvement of affinity due to the inclusion of multiple recognition units (multivalent effect) [ 20 , 21 , 55 , 56 , 57 , 58 , 59 ], the influence of chain length on affinity [ 60 , 61 ], and remote (heterovalent) recognition [ 59 ].…”

“…Wang et al demonstrated the differences of each N -glycan branch in lectin recognition by comprehensive interaction analysis of various N -glycans with several lectins using a glycan array [ 53 , 54 ]. Plant-derived Sambucus nigra lectin (SNA), which recognizes sialic acid, recognized the sialic acid on the α1,3-branched chain more strongly than the sialic acid on the α1,6-branched chain.…”