Synthesis of Lipid-Linked Oligosaccharides (LLOs) and Their Phosphonate Analogues as Probes To Study Protein Glycosylation Enzymes

Here we review chemical and chemoenzymatic methods for the synthesis of lipid-linked oligosaccharides (LLOs) and their phosphonate analogues, which serve as substrates and inhibitors to investigate the structure and mechanism of protein N -glycosylation enzymes. We emphasize how to overcome the challenges pertaining to the instability and difficult physicochemical properties of this class of compounds. 1 Introduction 2 LLO Syntheses 2.1 Glycosyl Phosphate Syntheses 2.2 Glycosyl Phosphonates 2.3 Lipid Elongation 2.4 Lipid Phosphates 2.5 Coupling Reaction Strategies 3 Chemoenzymatic Synthesis of Elongated LLOs 4 Biological Properties of Synthetic LLOs 5 Conclusion