Emerging Trends in Glycoscience, Part #2

Sialic acids (Sias) are monosaccharides belonging to a subfamily of nonulosonic acids (NulOs), which are nine-carbon alpha-keto acids found in nature. Sias are expressed by animals of the deuterostome lineage and by some pathogenic bacteria. They are the terminal residues on sialosides including sialyl glycans and sialyl glycoconjugates which play important roles in molecular recognition in biological systems. Sialosides in natural are structurally diverse with variations on the sialic acid forms (more than 50 have been found in nature), sialyl linkages, and underlying glycan and glycoconjugate structures. Sialosides containing natural occurring and non-natural modifications on the sialic acids are being developed as novel probes, potential diagnostics and therapeutics. An efficient strategy to access these biomedically important synthetic targets is chemoenzymatic synthesis. Sialyltransferase-catalyzed enzymatic sialylation of diverse underlying structures that are synthesized by chemical or chemoenzymatic approaches is increasingly implemented in a growing number of laboratories. This talk will discuss strategies for developing streamlined chemoenzymatic synthesis of complex sialoside targets with the consideration of chemoenzymatic synthetic process design, the design and the synthesis of sialyltransferase acceptor substrates, and enzyme engineering.

From the building blocks of nature to disease-battling pharmaceuticals, carbohydrates have had a profound impact on evolution, society, economy, and human health. Numerous applications of these essential biomolecules in many areas of science and technology exist, most of which can be found at the forefront of therapeutic agent and diagnostic platform development. Although carbohydrates are desirable for the pharmaceutical and biomedical communities, these molecules are very challenging targets for chemists because of the need for functionalization, protecting and leaving group manipulations, controlling anomeric stereoselectivity, separation, and analysis. The development of practical methods for the synthesis of building blocks, chemical glycosylation, and glycan assembly represent demanding areas of research. At the core of this presentation is the development of new methods, strategies, and technologies for chemical synthesis of glycans. These tools will be discussed along with recent results related to the development of new glycosylation reactions, methods for controlling stereoselectivity, and HPLC-based automated synthesis. The effectiveness of methods developed will be illustrated by the synthesis of glycopharmaceuticals. This work has been generously supported by grants from the National Institutes of Health.