Synthetic glycosylphosphatidylinositol (GPI) anchors

how these complex molecules have been made

Andrei V. Nikolaev, Nawaf Al-Maharik

    Research output: Contribution to journalReview article

    26 Citations (Scopus)

    Abstract

    Glycosylphosphatidylinositols (GPIs) are a class of natural glycosylphospholipids that anchor proteins, glycoproteins and lipophosphoglycans to the membrane of eukaryotic cells. GPI anchors are widely present in parasitic protozoa, where GPI-anchored mucins and phosphoglycans are abundant and form a dense protective layer (glycocalyx) on the surface of the parasites. This type of anchor appears to be present in these organisms with a much higher frequency than in higher eukaryotes. Since the first full assignment of a GPI structure in 1988, more than 50 glycosylphosphatidylinositols have been structurally characterised. The functions of GPI anchors (in addition to the clear one of linking the above biopolymers to membranes) have been extensively discussed. The high lateral mobility of GPIs and GPI-anchored polymers seems to actively facilitate the selective release of molecules from the cell surface and the exchange of membrane proteins between cells. There is also evidence that GPIs and/ or their metabolites can act as secondary messengers, modulating biological events including insulin production, insulin-mediated signal transduction, cellular proliferation and cell-cell recognition. Their discovered role as mediators of regulatory processes makes the chemical preparation of these compounds and their analogues of great interest. This comprehensive review highlights the progress in the chemical synthesis of GPI anchors and related glycoconjugate structures from protozoan parasites, yeast and mammals in the last two decades. The synthesis of a structurally related prokaryotic glycoconjugate of Mycobacterium tuberculosis is also discussed.

    Original languageEnglish
    Pages (from-to)970-1020
    Number of pages51
    JournalNatural Product Reports
    Volume28
    Issue number5
    DOIs
    Publication statusPublished - 2011

    Keywords

    • CELL-SURFACE GLYCANS
    • RAT-BRAIN THY-1
    • BACILLUS-CALMETTE-GUERIN
    • TRYPANOSOMA-BRUCEI
    • CONVERGENT SYNTHESIS
    • MEMBRANE ANCHOR
    • PHOSPHATIDYLINOSITOL MANNOSIDES
    • ENANTIOMERICALLY PURE
    • CHEMICAL-SYNTHESIS
    • TOXOPLASMA-GONDII

    Cite this

    Nikolaev, Andrei V. ; Al-Maharik, Nawaf. / Synthetic glycosylphosphatidylinositol (GPI) anchors : how these complex molecules have been made. In: Natural Product Reports. 2011 ; Vol. 28, No. 5. pp. 970-1020.
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    abstract = "Glycosylphosphatidylinositols (GPIs) are a class of natural glycosylphospholipids that anchor proteins, glycoproteins and lipophosphoglycans to the membrane of eukaryotic cells. GPI anchors are widely present in parasitic protozoa, where GPI-anchored mucins and phosphoglycans are abundant and form a dense protective layer (glycocalyx) on the surface of the parasites. This type of anchor appears to be present in these organisms with a much higher frequency than in higher eukaryotes. Since the first full assignment of a GPI structure in 1988, more than 50 glycosylphosphatidylinositols have been structurally characterised. The functions of GPI anchors (in addition to the clear one of linking the above biopolymers to membranes) have been extensively discussed. The high lateral mobility of GPIs and GPI-anchored polymers seems to actively facilitate the selective release of molecules from the cell surface and the exchange of membrane proteins between cells. There is also evidence that GPIs and/ or their metabolites can act as secondary messengers, modulating biological events including insulin production, insulin-mediated signal transduction, cellular proliferation and cell-cell recognition. Their discovered role as mediators of regulatory processes makes the chemical preparation of these compounds and their analogues of great interest. This comprehensive review highlights the progress in the chemical synthesis of GPI anchors and related glycoconjugate structures from protozoan parasites, yeast and mammals in the last two decades. The synthesis of a structurally related prokaryotic glycoconjugate of Mycobacterium tuberculosis is also discussed.",
    keywords = "CELL-SURFACE GLYCANS, RAT-BRAIN THY-1, BACILLUS-CALMETTE-GUERIN, TRYPANOSOMA-BRUCEI, CONVERGENT SYNTHESIS, MEMBRANE ANCHOR, PHOSPHATIDYLINOSITOL MANNOSIDES, ENANTIOMERICALLY PURE, CHEMICAL-SYNTHESIS, TOXOPLASMA-GONDII",
    author = "Nikolaev, {Andrei V.} and Nawaf Al-Maharik",
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    doi = "10.1039/c0np00064g",
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    Synthetic glycosylphosphatidylinositol (GPI) anchors : how these complex molecules have been made. / Nikolaev, Andrei V.; Al-Maharik, Nawaf.

    In: Natural Product Reports, Vol. 28, No. 5, 2011, p. 970-1020.

    Research output: Contribution to journalReview article

    TY - JOUR

    T1 - Synthetic glycosylphosphatidylinositol (GPI) anchors

    T2 - how these complex molecules have been made

    AU - Nikolaev, Andrei V.

    AU - Al-Maharik, Nawaf

    PY - 2011

    Y1 - 2011

    N2 - Glycosylphosphatidylinositols (GPIs) are a class of natural glycosylphospholipids that anchor proteins, glycoproteins and lipophosphoglycans to the membrane of eukaryotic cells. GPI anchors are widely present in parasitic protozoa, where GPI-anchored mucins and phosphoglycans are abundant and form a dense protective layer (glycocalyx) on the surface of the parasites. This type of anchor appears to be present in these organisms with a much higher frequency than in higher eukaryotes. Since the first full assignment of a GPI structure in 1988, more than 50 glycosylphosphatidylinositols have been structurally characterised. The functions of GPI anchors (in addition to the clear one of linking the above biopolymers to membranes) have been extensively discussed. The high lateral mobility of GPIs and GPI-anchored polymers seems to actively facilitate the selective release of molecules from the cell surface and the exchange of membrane proteins between cells. There is also evidence that GPIs and/ or their metabolites can act as secondary messengers, modulating biological events including insulin production, insulin-mediated signal transduction, cellular proliferation and cell-cell recognition. Their discovered role as mediators of regulatory processes makes the chemical preparation of these compounds and their analogues of great interest. This comprehensive review highlights the progress in the chemical synthesis of GPI anchors and related glycoconjugate structures from protozoan parasites, yeast and mammals in the last two decades. The synthesis of a structurally related prokaryotic glycoconjugate of Mycobacterium tuberculosis is also discussed.

    AB - Glycosylphosphatidylinositols (GPIs) are a class of natural glycosylphospholipids that anchor proteins, glycoproteins and lipophosphoglycans to the membrane of eukaryotic cells. GPI anchors are widely present in parasitic protozoa, where GPI-anchored mucins and phosphoglycans are abundant and form a dense protective layer (glycocalyx) on the surface of the parasites. This type of anchor appears to be present in these organisms with a much higher frequency than in higher eukaryotes. Since the first full assignment of a GPI structure in 1988, more than 50 glycosylphosphatidylinositols have been structurally characterised. The functions of GPI anchors (in addition to the clear one of linking the above biopolymers to membranes) have been extensively discussed. The high lateral mobility of GPIs and GPI-anchored polymers seems to actively facilitate the selective release of molecules from the cell surface and the exchange of membrane proteins between cells. There is also evidence that GPIs and/ or their metabolites can act as secondary messengers, modulating biological events including insulin production, insulin-mediated signal transduction, cellular proliferation and cell-cell recognition. Their discovered role as mediators of regulatory processes makes the chemical preparation of these compounds and their analogues of great interest. This comprehensive review highlights the progress in the chemical synthesis of GPI anchors and related glycoconjugate structures from protozoan parasites, yeast and mammals in the last two decades. The synthesis of a structurally related prokaryotic glycoconjugate of Mycobacterium tuberculosis is also discussed.

    KW - CELL-SURFACE GLYCANS

    KW - RAT-BRAIN THY-1

    KW - BACILLUS-CALMETTE-GUERIN

    KW - TRYPANOSOMA-BRUCEI

    KW - CONVERGENT SYNTHESIS

    KW - MEMBRANE ANCHOR

    KW - PHOSPHATIDYLINOSITOL MANNOSIDES

    KW - ENANTIOMERICALLY PURE

    KW - CHEMICAL-SYNTHESIS

    KW - TOXOPLASMA-GONDII

    U2 - 10.1039/c0np00064g

    DO - 10.1039/c0np00064g

    M3 - Review article

    VL - 28

    SP - 970

    EP - 1020

    JO - Natural Product Reports

    JF - Natural Product Reports

    SN - 0265-0568

    IS - 5

    ER -