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388 17 Enzymatic Generation of Sialoconjugate Diversity

17.3.6
Biomedical Applications of Sialoconjugate Arrays
Owing to the highly complex structure of oligosaccharides and their multiple
biological function, glycans and their receptors have become important targets to
improve our understanding of cellular physiology, for example, in cell adhesion,
recognition, signaling, or pathogenic infection, as well as for the development
of novel therapeutic strategies. In the last decade, carbohydrate microarrays have
therefore become core technologies for analyzing carbohydrate-mediated recogni-
tion events in a high-throughput manner [79]. Carbohydrate arrays can provide
facile analyses of carbohydrate-binding proteins, antibodies in serum, and enzyme
activities with minimal quantities of saccharide samples.
Particularly, many glycan-binding proteins in animals and pathogens recognize
sialic acid or its modified forms in sialoconjugates, but their mode of molecular
recognition and the biological importance of modified sialic acids in protein–glycan
interactions are poorly understood. The recent advances made in the chemoen-
zymatic synthesis of sialoconjugates in vitro and the microarray-based technology
of glycans immobilized to a solid chip surface will help profoundly in the rapid
analysis of the binding properties of a variety of sialoconjugate-binding partners
including identification of disease-related anti-glycan lectins and antibodies for
diagnosis, detection of pathogens and cells, the quantitative measurements of
glycan–protein interactions, as well as the fast assessment of substrate specificities
of GTs. For example, using glycan microarray technology, diverse sialic acids or
their derivatives have been displayed as conjugates on the Gal moiety of glycan
acceptors for the screening of SiaT epitope specificities [80], identification of high-
affinity Siglec ligands [78], revealing novel interactions of modified sialic acids with
proteins and viruses [41, 81], and analysis of biointerfaces for protein binding.
These early results demonstrate the potential utility of the synthetic sialoconjugate
diversity for the further development of promising diagnostic tools based on car-
bohydrate arrays for infectious disease detection, cancer monitoring, and vaccine
development.

17.4
Conclusions

While enzymatic methods for glycoside synthesis have become a serious competi-
tion for chemical routes in general, enzymatic sialylation has long been recognized
as the gold standard in the field because of the inadequacy of chemical approaches
of stereoselective sialoside formation. Cascade enzyme processes are especially
important for GT-catalyzed reactions because they require nucleotide-activated
substrates that are highly expensive and unstable but can be generated in situ from
simpler starting materials using standard biosynthetic enzymes. This survey of the
current state of the art shows that there is good progress made for crafting the