Probing Trypanosoma brucei glycosylphosphatidylinositol biosynthesis using novel precursor-analogues

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    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

    Cite this

    @article{ccf5544ea9144d8ea2d89058c0997501,
    title = "Probing Trypanosoma brucei glycosylphosphatidylinositol biosynthesis using novel precursor-analogues",
    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.",
    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",
    author = "Urbaniak, {Michael D.} and Arthur Crossman and Ferguson, {Michael A. J.}",
    year = "2008",
    month = "8",
    doi = "10.1111/j.1747-0285.2008.00688.x",
    language = "English",
    volume = "72",
    pages = "127--132",
    journal = "Chemical Biology & Drug Design",
    issn = "1747-0277",
    publisher = "Wiley",
    number = "2",

    }

    Probing Trypanosoma brucei glycosylphosphatidylinositol biosynthesis using novel precursor-analogues. / Urbaniak, Michael D.; Crossman, Arthur; Ferguson, Michael A. J.

    In: Chemical Biology & Drug Design, Vol. 72, No. 2, 08.2008, p. 127-132.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Probing Trypanosoma brucei glycosylphosphatidylinositol biosynthesis using novel precursor-analogues

    AU - Urbaniak, Michael D.

    AU - Crossman, Arthur

    AU - Ferguson, Michael A. J.

    PY - 2008/8

    Y1 - 2008/8

    N2 - 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.

    AB - 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.

    KW - glycolipid

    KW - glycosylphosphatidylinositol

    KW - steriodal

    KW - substrate analogue

    KW - Trypanosoma brucei

    KW - AFRICAN SLEEPING SICKNESS

    KW - DE-N-ACETYLASE

    KW - MEMBRANE ANCHOR BIOSYNTHESIS

    KW - GPI BIOSYNTHESIS

    KW - SUBSTRATE-SPECIFICITY

    KW - INOSITOL-ACYLATION

    KW - PATHWAY

    KW - PARASITE

    KW - CELLS

    KW - PROTEINS

    U2 - 10.1111/j.1747-0285.2008.00688.x

    DO - 10.1111/j.1747-0285.2008.00688.x

    M3 - Article

    VL - 72

    SP - 127

    EP - 132

    JO - Chemical Biology & Drug Design

    JF - Chemical Biology & Drug Design

    SN - 1747-0277

    IS - 2

    ER -