CHAPTER 9: Synthetic Studies of GPI-Anchored Peptides, Glycopeptides, and Proteins

Glycosylphosphatidylinositols (GPIs) are complex glycolipids, which anchor surface proteins and glycoproteins onto the cell membrane. To study the biological functions of GPI-anchored proteins and glycoproteins, it is essential to have access to these biomolecules in structurally well-defined forms and sufficient quantity. Accordingly, several synthetic strategies for these molecules based on regioselective chemical condensation, native chemical ligation (NCL), and enzymatic ligation of synthetic GPI anchors with peptides, glycopeptides and proteins have been established. In the meantime, effective strategies have also been developed for GPI-anchored proteomics analysis by using GPI-binding bacterial toxin or cell-surface GPI-anchor metabolic engineering techniques to simplify GPI-anchored protein pull-down. These studies have greatly facilitated the access to and understanding of GPI-anchored proteins. This chapter reviews the significant progress in these areas, as well as in the biosynthesis of GPIs and GPI-anchored proteins.