Chemical Biology of Glycosylphosphatidylinositol Anchors

Glycosylphosphatidylinositols (GPIs) are complex glycolipids that are covalently linked to the C‐terminus of proteins as a posttranslational modification. They anchor the attached protein to the cell membrane and are essential for normal functioning of eukaryotic cells. GPI‐anchored proteins are structurally and functionally diverse. Many GPIs have been structurally characterized but comprehension of their biological functions, beyond the simple physical anchoring, remains largely speculative. Work on functional elucidation at a molecular level is still limited. This Review focuses on the roles of GPI unraveled by using synthetic molecules and summarizes the structural diversity of GPIs, as well as their biological and chemical syntheses. Protein anchors: Glycosylphosphatidylinositol (GPI) glycolipids anchor proteins on the extracellular membrane. This mode of protein posttranslational modification is common and important in eukaryotes. Insight into the structure and function of GPIs is discussed, with an emphasis on the recent progress in using structurally defined synthetic GPIs as tools to dissect their biological functions.