Glycan arrays: recent advances and future challenges

Abstract

Carbohydrate arrays, also referred to as glycan arrays, are composed of various oligosaccharides and/or polysaccharides immobilized on a solid support in a spatially defined arrangement. This technology provides a powerful, high-throughput approach to examining carbohydrate-macromolecule interactions, and glycan arrays have had a significant impact on the field of glycobiology. This review focuses on recent advances in glycan array technology, limitations, and opportunities for improvement. In particular, new methods for the production of natural glycan arrays and chemoenzymatic approaches are greatly expanding the diversity of structures on arrays. Since multivalent complex formation is generally required to achieve tight binding, methods to evaluate and modulate presentation are vital for enhancing the capabilities of this technology.

Figure 1

Carbohydrate-macromolecule interactions (a) Interaction of carbohydrate binding proteins and macromolecules with cell surface glycans presented on glycoproteins and glycolipids. (b) Optimal spacing and orientation of carbohydrate ligands is critical to achieve high avidity multivalent binding.

Figure 2

Examples of approaches to expanding structural diversity on glycan arrays. (a) Reductive amination with fluorescent tags facilitate purification and immobilization of isolated natural glycans but results in ring-opening of the reducing end sugar. (b) Formation of hydrazones and oximes with the reducing end sugar enables surface immobilization of glycans via linkers and can afford ring-closed products. (c) Covalent immobilization of underivatized glycans to photoactive surfaces such as phthalimidefunctionalized surfaces.