Automated glycan assembly of Lewis type I and II oligosaccharide antigens

Abstract

Lewis antigens are fucosylated oligosaccharides that play crucial roles in various biological processes. Here, we illustrate how automated glycan assembly (AGA) provides quick access to a series of more than ten defined Lewis type-I and type-II antigens.

Automated Glycan Assembly: A Perspective

“…36 Efficient branching strategies facilitated access to lactoside oligosaccharides, including blood-group related Lewis antigens and tumor-associated carbohydrate antigens. 29,55 Many glycans found on microorganisms were obtained by AGA: Polyglucosides such as α-, β-glucans and dextran; 36,50 GlcNAc oligomers like chitin and β-1,6-poly- N -acetylglucosamine (PNAG); 50 mycobacterial arabinofuranosides; 56 α-oligorhamnans; 57 and α-mannans. 25,50 Moreover, AGA was used to synthesize defined portions of the capsular polysaccharides (CPSs) of Streptococcus pneumoniae serotypes 3 and 8.…”

Enzymatic Building‐Block Synthesis for Solid‐Phase Automated Glycan Assembly

“…In summary, we have demonstrated that selectively protected and activated building blocks can be generated by biocatalysis at gram scale, exploiting the promiscuity of carbohydrate‐active enzymes. The short and efficient synthesis can be scaled up to provide reagents for automated solid‐phase glycan assembly [1, 3, 6] . As microbial glycosyltransferases are becoming more accessible and are increasingly shown to be tolerant to protecting and activating groups, this chemoenzymatic strategy should be a useful addition to modern carbohydrate synthesis.…”

“…Oligoand polysaccharides and their conjugates are important targets for chemical synthesis and a number of automated approaches have recently been developed in this field, including solid-phase synthesis, HPLC-assisted synthesis, fluorous-tag solvent-phase synthesis and artificial Golgi apparatus. [1][2][3][4][5][6][7][8][9] The formation of glycosidic linkages can either be achieved through biocatalysis using carbohydrate active enzymes or by chemical methods, which require selective protection and activation. The main strength of the enzymatic approach is scalability due to low numbers of steps, whereas chemical methods give access to a much broader range of natural and unnatural targets, while limited by the availability of complex, differentially protected building blocks.…”

Multivalent glycan arrays

“…The coupling cycle, consisting of glycosylation, capping, and deprotection, has been optimized to achieve nearly quantitative conversion in around 1.5 h. 36,37 Moreover, the glycan is attached to the solid support through a linker that, upon UV irradiation, liberates the target glycan already equipped with an amino-linker for subsequent surface functionalization. 38 Collections of natural and unnatural glycans found applications in vaccine development, 39,40 materials science, 36,41,42 and structural studies 37 (see Fig. 2).…”