Probing Trypanosoma brucei glycosylphosphatidylinositol biosynthesis using novel precursor-analogues

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    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 languageEnglish
    Pages (from-to)127-132
    Number of pages6
    JournalChemical Biology & Drug Design
    Volume72
    Issue number2
    DOIs
    Publication statusPublished - 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

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