Inhibitors of GPI biosynthesis

Glycosylphosphatidylinositol (GPI) is a complex glycolipid structure that acts as a membrane anchor for many cell-surface proteins of eukaryotes. The increasing number of completed genomes, has allowed considerable progress in the molecular characterisation of GPI biosynthesis, not only in terms of human diseases, but also of pathogenic eukaryotic organisms. Although the GPI core glycan is conserved in all organisms, many differences in additional modifications to GPI structures and biosynthetic pathways have been reported. The specificities of these biosynthesic steps must be investigated to allow exploitation of species-specific differences for drug development, however, detailed enzymological studies to date have been limited. Consequently, despite the conserved GPI core structure, the GPI biosynthetic machinery is different enough between humans and a wide range of eukaryotic pathogens to represent a rich seam of potential therapeutic targets.
Here we review the recent and promising progress in the field of GPI inhibition.