Chemical synthesis, modification and mimicry of the GPI anchor

Glycophosphatidylinositol (GPI) anchors are complex glycolipids which typically anchor extracellular proteins onto the lipid membranes of eukaryotic cells. Although providing a natural platform in which to present or transfer functional molecules onto cells and viruses, GPI anchors are difficult biologics to generate in a homogenously pure form. It is also difficult, though not impossible, to elucidate and confirm their structures unambiguously. Today, chemical synthesis offers not only the versatility to make both complex and simplified GPI mimics and tools, but also the means to directly relate an exact GPI structure to its biological function. These synthetic GPIs may be further modified to allow the chemical attachment of any functional molecule, and not solely proteins, in a biologically compatible manner. Fluorescent labels and affinity tags can be exploited to investigate a particular biological response or process. Alternatively, synthetic glycans of GPI anchors can be employed to elicit a particular immune response or to generate GPI-specific antibodies. In this chapter, we shall overview the structure and synthesis of GPI anchors, and give perspectives on the biological study and therapeutic potential of synthetically-derived GPI biologics.