Chemical Regulation of Glycosylation Processes

Abstract

Glycans (monosaccharides and oligosaccharides) and their conjugates (glycoproteins, glycolipids, and proteoglycans) are structurally diverse biomolecules that are involved in many biological processes of health and disease. The structural diversity of glycans and glycoconjugates is owed to their monosaccharide composition, anomeric state, glycosidic linkage, modification (phosphorylation, sulfation, acetylation, etc.) and aglycone (protein, lipid, etc.). These diverse structures are controlled by complex glycosylation processes in cells, which are mediated by various glycosyltransferases and glycosidases. Glycosylation processes can be chemically regulated by inhibition of glycosyltransferases or glycosidases with natural and synthetic molecules. Treatment of cells with inhibitors of these enzymes results in the production of glycans or glycoconjugates containing missing or altered glycan chains. This approach is highly useful for examining the potential functional role(s) of glycans and glycoconjugates in cells or tissues, and in biological processes of health and disease. Eventually, it will provide novel mechanisms for disease treatment. This review highlights recent developments in chemical regulation of glycosylation processes with specific targets including: inhibition of (1) N-glycosylation, (2) O-glycosylation, (3) O-linked GlcNAc glycosylation, (4) proteoglycan biosynthesis, (5) glycolipid biosynthesis, and (6) terminal glycosylation. The goal of this review is to provide researchers with more competent choices in their research and lay a foundation on which continued advancements can be made to promote further explorations in glycoscience and biomedical research and applications.