Chemical Synthesis of GPIs and GPI‐Anchored Glycopeptides

Guo, Zhongwu; Bishop, Lee M.

doi:10.1002/ejoc.200400198

Cited by 45 publications

(21 citation statements)

References 60 publications

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“…39 To accomplish the former task, inositol derivative 8 was prepared using a delayed 1,6- O -differentiation route in combination with chemical enantiomeric resolution. To achieve α-glycosylation with acceptable selectivity in the pseudodisaccharide formation, 2-azido-2-deoxy-D-glucosyl donors were employed as latent glucosamine units due to the nonparticipating property of the 2-azido group.…”

Section: Resultsmentioning

confidence: 99%

Chemical synthesis and functionalization of clickable glycosylphosphatidylinositol anchors

Swarts

Guo

2011

Chem. Sci.

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Glycosylphosphatidylinositol (GPI) anchorage is a common posttranslational modification of eukaryotic proteins. Chemical synthesis of structurally defined GPIs and GPI derivatives is a necessary step toward understanding the properties and functions of these molecules in biological systems. In this work, the synthesis of several functionalized GPI anchors was accomplished using the para-methoxybenzyl (PMB) group for permanent hydroxyl protection, which allowed the incorporation of functionalities that are incompatible with permanent protecting groups traditionally used in carbohydrate synthesis. A flexible convergent-divergent assembly strategy enabled efficient access to a diverse set of target structures, including “clickable” Alkynyl-GPIs 1 and 2 and Azido-GPI 3. For global deprotection, a one-pot reaction was employed to afford the target GPIs in excellent yields (85-97%). Fully deprotected clickable GPIs 2 and 3 were readily conjugated to imaging and affinity probes via Cu(I)-catalyzed and Cu-free strain-promoted [3+2] cycloaddition, respectively, resulting in GPI-Fluor 4 and GPI-Biotin 5.

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Section: Resultsmentioning

confidence: 99%

Chemical synthesis and functionalization of clickable glycosylphosphatidylinositol anchors

Swarts

Guo

2011

Chem. Sci.

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“…Several total syntheses of native GPI anchors have been reported; however, these routes are complicated and not amenable to structural modification (reviewed in ref (60)). More importantly, most synthetic routes do not provide an avenue for coupling the anchor structure to a protein, the state in which they function naturally (60). Recently, Shao et al attached a synthetic 12-amino acid glycopeptide from CD52, a GPI-anchored peptide, to a synthetically produced GPI anchor (61).…”

Section: Structural Significance Of the Gpi Anchormentioning

confidence: 99%

The Glycosylphosphatidylinositol Anchor: A Complex Membrane-Anchoring Structure for Proteins

2008

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Positioned at the C-terminus of many eukaryotic proteins, the glycosylphosphatidylinositol (GPI) anchor is a posttranslational modification that anchors the modified protein in the outer leaflet of the cell membrane. The GPI anchor is a complex structure comprising a phosphoethanolamine linker, glycan core, and phospholipid tail. GPI-anchored proteins are structurally and functionally diverse and play vital roles in numerous biological processes. While several GPI-anchored proteins have been characterized, the biological functions of the GPI anchor have yet to be elucidated at a molecular level. This review discusses the structural diversity of the GPI anchor and its putative cellular functions, including involvement in lipid raft partitioning, signal transduction, targeting to the apical membrane, and prion disease pathogenesis. We specifically highlight studies in which chemically synthesized GPI anchors and analogues have been employed to study the roles of this unique posttranslational modification.

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“…[7b] Evaluating the consequences of lipid structural variations on GPI-AP trafficking, surface localization, and antibody binding can be aided by chemical synthesis, which is an invaluable approach to obtaining structurally defined GPI anchors for biological study. [14] …”

Section: Introductionmentioning

confidence: 99%

Total Synthesis of a Glycosylphosphatidylinositol Anchor of the Human Lymphocyte CD52 Antigen

Srinivas

Swarts

Guo

2011

Chemistry A European J

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The first total synthesis of a glycosylphosphatidylinositol (GPI) anchor bearing a polyunsaturated arachidonoyl fatty acid is reported. This lipid is found in mammalian GPIs that do not undergo lipid remodeling, a process that has important implications in the localization and function of GPI-anchored proteins. Incorporation of this oxidation- and reduction-sensitive lipid in the target GPI was accomplished using the para-methoxybenzyl (PMB) group for permanent hydroxyl group protection, which featured a selective, rapid, and efficient global deprotection protocol. The flexibility of this synthetic strategy was further highlighted by the inclusion of two additional GPI core structural modifications present in the GPI anchor of the human lymphocyte CD52 antigen.

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Chemical Synthesis of GPIs and GPI‐Anchored Glycopeptides

Cited by 45 publications

References 60 publications

Chemical synthesis and functionalization of clickable glycosylphosphatidylinositol anchors

Chemical synthesis and functionalization of clickable glycosylphosphatidylinositol anchors

The Glycosylphosphatidylinositol Anchor: A Complex Membrane-Anchoring Structure for Proteins

Total Synthesis of a Glycosylphosphatidylinositol Anchor of the Human Lymphocyte CD52 Antigen

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