Multi-dimensional glycan microarrays with glyco-macroligands

Abstract

Glycan microarray has become a powerful high-throughput tool for examining binding interactions of carbohydrates with the carbohydrate binding biomolecules like proteins, enzymes, antibodies etc. It has shown great potential for biomedical research and applications, such as antibody detection and profiling, vaccine development, biomarker discovery, and drug screening. Most glycan microarrays were made with monovalent glycans immobilized directly onto the array surface via either covalent or non-covalent bond, which afford a multivalent glycans in two dimensional (2D) displaying. A variety of glyco-macroligands have been developed to mimic multivalent carbohydrate-protein interactions for studying carbohydrate-protein interactions and biomedical research and applications. Recently, a number of glyco-macroligands have been explored for glycan microarray fabrication, in particular to mimick the three dimensional (3D) multivalent display of cell surface carbohydrates. This review highlights these recent developments of glyco-macroligand-based microarrays, predominantly, novel glycan microarrays with glyco-macroligands like glycodendrimers, glycopolymers, glycoliposomes, neoglycoproteins, and glyconanoparticles with the effort in controlling the density and orientation of glycans on the array surface, which facilitate both their binding specificity and affinity and thus the high performance of glycan microarrays.

Design, Synthetic Strategies, and Therapeutic Applications of Heterofunctional Glycodendrimers

“…Therefore, and not surprisingly, the field of glycodendrimers, with their intrinsic multivalency and high affinity (avidity), has been exploited in the creation of powerful tools to provide therapeutic applications against cancer [44] that also include theranostics [45]. Several strategies can be applied to address this issue, amongst which, immune cell targeting through their well-studied mannoside receptors such as DC-SIGN [10], anti-carbohydrate antibodies and vaccines [40][41][42][43][44], screening microarrays using dendrimer's increased sensitivity [46,47], and notably anti-cancer vaccines. Interestingly, to this arsenal of glycodendrimers of therapeutic values against cancer, there is an additional avenue that was recently investigated.…”

Glycomaterials for probing host–pathogen interactions and the immune response

“…Currently, efforts utilizing the principles of macromolecular design are underway to recapitulate the nanoscale three-dimensional presentation of glycans at the cell surface in arrays in order to carefully curate and preserve the contributions of parameters, such as glycan valency and density, on the specificity of glycan recognition (Figure 2(c)). 24,29 …”

Notable Aspects of Glycan-Protein Interactions

“…Several approaches have been successfully applied for increasing glycans multivalency on the microarrays. The glycans can be conjugated to a polymer core (glycopolymers) a protein core (neoglycoproteins), nanoparticles (glyconanoparticles), liposomes (glycoliposomes), or dendrimers (glycodendrimers) [ 106 , 107 ]. To address the issue of glycan heterogeneity in nature, glycans extracts from biological samples are purified, fluorescently tagged, and printed on the array.…”