Targeting the GPI biosynthetic pathway

Pathogens and Global Health
Usha Yadav, Mohd Ashraf Khan

Abstract

The GPI (Glycosylphosphatidylinositol) biosynthetic pathway is a multistep conserved pathway in eukaryotes that culminates in the generation of GPI glycolipid which in turn anchors many proteins (GPI-APs) to the cell surface. In spite of the overall conservation of the pathway, there still exist subtle differences in the GPI pathway of mammals and other eukaryotes which holds a great promise so far as the development of drugs/inhibitors against specific targets in the GPI pathway of pathogens is concerned. Many of the GPI structures and their anchored proteins in pathogenic protozoans and fungi act as pathogenicity factors. Notable examples include GPI-anchored variant surface glycoprotein (VSG) in Trypanosoma brucei, GPI-anchored merozoite surface protein 1 (MSP1) and MSP2 in Plasmodium falciparum, protein-free GPI related molecules like lipophosphoglycans (LPGs) and glycoinositolphospholipids (GIPLs) in Leishmania spp., GPI-anchored Gal/GalNAc lectin and proteophosphoglycans in Entamoeba histolytica or the GPI-anchored mannoproteins in pathogenic fungi like Candida albicans. Research in this active area has already yielded encouraging results in Trypanosoma brucei by the development of parasite-specific inhibitors of GlcNCONH...Continue Reading

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Citations

May 1, 2020·FEMS Yeast Research·Dongmei LiRichard Calderone
Aug 23, 2020·Toxins·Amanda Pissinatti CanelliMaurício Ventura Mazzi
Dec 12, 2019·Frontiers in Microbiology·Soraia L LimaJoão N de Almeida Junior
Jul 22, 2020·Journal of Medicinal Chemistry·Wei LiuShengzheng Wang

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