Sweet spots in functional glycomics

Abstract

Information contained in the mammalian glycome is decoded by glycan-binding proteins (GBPs) that mediate diverse functions including host-pathogen interactions, cell trafficking and transmembrane signaling. Although information on the biological roles of GBPs is rapidly expanding, challenges remain in identifying the glycan ligands and their impact on GBP function. Protein-glycan interactions are typically low affinity, requiring multivalent interactions to achieve a biological effect. Though many glycoproteins can carry the glycan structure recognized by the GBP, other factors, such as recognition of protein epitopes and microdomain localization, may restrict which glycoproteins are functional ligands in situ. Recent advances in development of glycan arrays, synthesis of multivalent glycan ligands, bioengineering of cell-surface glycans and glycomics databases are providing new tools to identify the ligands of GBPs and to elucidate the mechanisms by which they participate in GBP function.

Pre-B cell receptor binding to galectin-1 modifies galectin-1/carbohydrate affinity to modulate specific galectin-1/glycan lattice interactions

“…These findings may be extrapolated to other haematopoietic cell niches where there is increasing evidence that galectin-glycan interactions control communication between haematopoietic and non-haematopoietic cells 46 . More generally, GAL/glycan lattices include many pharmaceutically relevant targets that cover biologically important processes, such as proliferation, migration or apoptosis 7,47 . In this regard, galectin inhibitors that block the CRD have been developed for cancer treatment [48][49][50] .…”

Extensive Determination of Glycan Heterogeneity Reveals an Unusual Abundance of High Mannose Glycans in Enriched Plasma Membranes of Human Embryonic Stem Cells

“…It is the most common and complex form of post-translational modification, with ϳ50% of all eukaryotic proteins glycosylated (1,2). A majority of glycans are found on the cell surface, where they are optimally poised to be the first cellular components encountered by approaching cells, pathogens, antibodies, or other molecules, as well as advertise information about the internal state and homeostasis of the cell (3,4). Therefore, glycans play an essential role in many biological processes, including cell development and differentiation, cell-cell or cell-matrix communication, and pathogen-host recognition (3,(5)(6)(7).…”

Synthesis and characterization of functional six-membered ring carbonates for the preparation of orthogonal couplers

“…This opens up potential application of these orthogonal coupler for the preparation of glycoconjugates like glycopolymers [38,39] or glycan arrays [40]. The preparation of glycoarrays is an example for surface functionalization under mild conditions [41,42]. …”