Synthesis of some second-generation substrate analogues of early intermediates in the biosynthetic pathway of glycosylphosphatidylinositol membrane anchors

Arthur Crossman Jr., John S. Brimacombe, Michael A. J. Ferguson, Terry K. Smith

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    18 Citations (Scopus)

    Abstract

    1-D-6-O-(2-Amino-2-deoxy-alpha-D-glucopyranosyl)-2-O-octyl-myo-inositol 1-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate) (23) and the corresponding 2-O-hexadecyl-D-myo-inositol compound 24 have been prepared as substrate analogues of an early intermediate in the biosynthetic pathway of glycosylphosphatidylinositol (GPI) membrane anchors. 1-D-6-O-(2-Amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 1-(1,2-di-O-octyl-sn-glycerol 3-phosphate) has also been prepared as a substrate analogue. Biological evaluation of the analogues 23 and 24 revealed that they are neither substrates nor inhibitors of GPI biosynthetic enzymes in the human (HeLa) cell-free system but are potent inhibitors at different stages of GPI biosynthesis in the Trypanosoma brucei cell-free system. (C) 1999 Elsevier Science Ltd. All rights reserved.

    Original languageEnglish
    Pages (from-to)42-51
    Number of pages10
    JournalCarbohydrate Research
    Volume321
    Issue number1-2
    DOIs
    Publication statusPublished - 15 Sep 1999

    Cite this

    @article{79b937cd8d294175ba413f04a6068b91,
    title = "Synthesis of some second-generation substrate analogues of early intermediates in the biosynthetic pathway of glycosylphosphatidylinositol membrane anchors",
    abstract = "1-D-6-O-(2-Amino-2-deoxy-alpha-D-glucopyranosyl)-2-O-octyl-myo-inositol 1-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate) (23) and the corresponding 2-O-hexadecyl-D-myo-inositol compound 24 have been prepared as substrate analogues of an early intermediate in the biosynthetic pathway of glycosylphosphatidylinositol (GPI) membrane anchors. 1-D-6-O-(2-Amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 1-(1,2-di-O-octyl-sn-glycerol 3-phosphate) has also been prepared as a substrate analogue. Biological evaluation of the analogues 23 and 24 revealed that they are neither substrates nor inhibitors of GPI biosynthetic enzymes in the human (HeLa) cell-free system but are potent inhibitors at different stages of GPI biosynthesis in the Trypanosoma brucei cell-free system. (C) 1999 Elsevier Science Ltd. All rights reserved.",
    author = "{Crossman Jr.}, Arthur and Brimacombe, {John S.} and Ferguson, {Michael A. J.} and Smith, {Terry K.}",
    year = "1999",
    month = "9",
    day = "15",
    doi = "10.1016/S0008-6215(99)00170-6",
    language = "English",
    volume = "321",
    pages = "42--51",
    journal = "Carbohydrate Research",
    issn = "0008-6215",
    publisher = "Elsevier",
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    TY - JOUR

    T1 - Synthesis of some second-generation substrate analogues of early intermediates in the biosynthetic pathway of glycosylphosphatidylinositol membrane anchors

    AU - Crossman Jr., Arthur

    AU - Brimacombe, John S.

    AU - Ferguson, Michael A. J.

    AU - Smith, Terry K.

    PY - 1999/9/15

    Y1 - 1999/9/15

    N2 - 1-D-6-O-(2-Amino-2-deoxy-alpha-D-glucopyranosyl)-2-O-octyl-myo-inositol 1-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate) (23) and the corresponding 2-O-hexadecyl-D-myo-inositol compound 24 have been prepared as substrate analogues of an early intermediate in the biosynthetic pathway of glycosylphosphatidylinositol (GPI) membrane anchors. 1-D-6-O-(2-Amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 1-(1,2-di-O-octyl-sn-glycerol 3-phosphate) has also been prepared as a substrate analogue. Biological evaluation of the analogues 23 and 24 revealed that they are neither substrates nor inhibitors of GPI biosynthetic enzymes in the human (HeLa) cell-free system but are potent inhibitors at different stages of GPI biosynthesis in the Trypanosoma brucei cell-free system. (C) 1999 Elsevier Science Ltd. All rights reserved.

    AB - 1-D-6-O-(2-Amino-2-deoxy-alpha-D-glucopyranosyl)-2-O-octyl-myo-inositol 1-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate) (23) and the corresponding 2-O-hexadecyl-D-myo-inositol compound 24 have been prepared as substrate analogues of an early intermediate in the biosynthetic pathway of glycosylphosphatidylinositol (GPI) membrane anchors. 1-D-6-O-(2-Amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 1-(1,2-di-O-octyl-sn-glycerol 3-phosphate) has also been prepared as a substrate analogue. Biological evaluation of the analogues 23 and 24 revealed that they are neither substrates nor inhibitors of GPI biosynthetic enzymes in the human (HeLa) cell-free system but are potent inhibitors at different stages of GPI biosynthesis in the Trypanosoma brucei cell-free system. (C) 1999 Elsevier Science Ltd. All rights reserved.

    U2 - 10.1016/S0008-6215(99)00170-6

    DO - 10.1016/S0008-6215(99)00170-6

    M3 - Article

    VL - 321

    SP - 42

    EP - 51

    JO - Carbohydrate Research

    JF - Carbohydrate Research

    SN - 0008-6215

    IS - 1-2

    ER -