Inhibitors of glycosyl-phosphatidylinositol anchor biosynthesis.
Glycosyl-phosphatidylinositol (GPI) is a complex glycolipid structure that acts as a membrane anchor for many cell-surface proteins of eukaryotes. GPI-anchored proteins are particularly abundant in protozoa such as Trypanosoma brucei, Leishmania major, Plasmodium falciparum and Toxoplasma gondii, and represent the major carbohydrate modification of many cell-surface parasite proteins. Although the GPI core glycan is conserved in all organisms, many differences in additional modifications to GPI structures and biosynthetic pathways have been reported. Therefore, the characteristics of GPI biosynthesis are currently being explored for the development of parasite-specific inhibitors. In vitro and in vivo studies using sugars and substrate analogues as well as natural compounds have shown that it is possible to interfere with GPI biosynthesis at different steps in a species-specific manner. Here we review the recent and promising progress in the field of GPI inhibition.
de Macedo
Cristiana Santos
CS
Institut für Virologie, Zentrum für Hygiene und Med. Mikrobiologie, Philipps-Universität Marburg, Germany.
Shams-Eldin
Hosam
H
Smith
Terry K
TK
Schwarz
Ralph T
RT
Azzouz
Nahid
N
D000818:Animals; D002240:Carbohydrate Sequence; D004983:Ethanolamines / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D018320:Leishmania major / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism; D014122:Toxoplasma / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000378:metabolism
D004983:Ethanolamines; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D015800:Protozoan Proteins; C005448:phosphorylethanolamine