Current Medicinal Chemistry
Current Medicinal Chemistry
5 years ago

Protozoan parasites glycosylphosphatidylinositol anchors: structures, functions and trends for drug discovery.

Morotti ALM, Martins-Teixeira MB, Carvalho I
Glycosylphosphatidylinositol (GPI) anchors are complex molecules that support certain proteins in the outer leaflet of the cell membrane. The GPI anchor scaffold is comprised of a glycan core which contains a phosphoethanolamine linker and a phospholipid chain. GPI-anchored proteins are structurally and functionally diverse and play essential roles in several biological processes, in particular cell-cell interaction. Although all eukaryotes possess GPI anchors in their cell membrane, protozoan parasites use this anchorage much more frequently than higher eukaryotes. There is extensive evidence that parasites' GPI anchors are important for virulence and interaction with host cells, as well as their own survival and viability. Structural and biosynthetic pathway differences between many parasites and mammalian cells have been explored for further understanding about functions and importance of these molecules. Some GPI biosynthesis enzymes have been proposed as alternative targets for therapy against parasitic diseases. This review discusses concisely the main differences between parasitic and mammalian GPI anchor biosynthesis, and highlights the implications of structural variation. Moreover, advances in drug discovery based on GPI anchor structures and biosynthetic pathway are outlined.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28748758

DOI: PubMed:28748758

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