Abstract
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 At-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.
Original language | English |
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Pages (from-to) | 127-132 |
Number of pages | 6 |
Journal | Chemical Biology & Drug Design |
Volume | 72 |
Issue number | 2 |
DOIs | |
Publication status | Published - Aug 2008 |
Keywords
- glycolipid
- glycosylphosphatidylinositol
- steriodal
- substrate analogue
- Trypanosoma brucei
- AFRICAN SLEEPING SICKNESS
- DE-N-ACETYLASE
- MEMBRANE ANCHOR BIOSYNTHESIS
- GPI BIOSYNTHESIS
- SUBSTRATE-SPECIFICITY
- INOSITOL-ACYLATION
- PATHWAY
- PARASITE
- CELLS
- PROTEINS