Probing Trypanosoma brucei glycosylphosphatidylinositol biosynthesis using novel precursor-analogues.
Glycosylphosphatidylinositol precursor-analogues were synthesized in which the natural diacylglycerol lipid was replaced with either of two steroidal moieties. The ability of the steroidal glycosylphosphatidylinositol precursor-analogues to prime the glycosylphosphatidylinositol biosynthetic pathway was assessed in a trypanosomal cell-free system. The N-acetyl-D-glucosaminylphosphatidylinositol de-N-acetylase was only able to act upon the N-acetylglucosamine form of one of the two analogues. However, the glucosamine form of both analogues could be mannosylated, but neither were inositol-acylated nor modified with ethanolamine phosphate. The use of alternative groups, such as sterols, in place of the natural diacylglycerol lipid may enable the production of more drug-like, substrate-based inhibitors.
Urbaniak
Michael D
MD
Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
Crossman
Arthur
A
Ferguson
Michael A J
MA
D000818:Animals; D002474:Cell-Free System; D017261:Glycosylphosphatidylinositols / Q000096:biosynthesis* / Q000737:chemistry*; D015394:Molecular Structure; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry; D013379:Substrate Specificity; D014346:Trypanosoma brucei brucei / Q000378:metabolism*
D017261:Glycosylphosphatidylinositols; D013256:Steroids