The surface glycoconjugates of parasitic protozoa: potential targets for new drugs

Protozoan parasites are the cause of many disease in humans and their domestic livestock. Glycoconjugates (i.e. glycoproteins, glycolipids) on the cell surface of these extremely diverse and very primative eukaryotes play a crucial role in determining the specificity of the host-parasite interaction and in protecting the parasites within their respective hosts. These molecules frequently share a common structural feature in that they are attached to the plasma membrane via a glycosylphosphatidylinositol (GPI) glycolipid. While GPI protein-membrane anchors are ubiquitous among the eukaryotes, they are used with exceptionally high frequency in the protozoa. Some kinetopastid parasites also synthesise very high levels of GPI-related glycolipids that are not linked to protein. Thus GPI-anchored molecules or free GPI glycolipids send to dominate the cell surface molecular architecture of these organisms. The highly elevated levels and specialised nature of GPI metabolism in the kinetoplastid and other parasites suggests that the GPI biosynthetic pathway might be a good target for the development of new chemotherapeutic agents. This article reviews the wide range of functions that GPI protein anchors and GPI-related glycolipids are thought to perform in these organisms and some aspects of their biosynthesis.