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Soluble Adamantyl Glycosphingolipid Analogs as Probes of Glycosphingolipid Function

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Glycobiology Protocols

Part of the book series: Methods in Molecular Biology ((MIMB,volume 347))

Abstract

Despite the extensive structural characterization of glycosphingolipids (GSLs), their functions in cell physiology and pathobiology remain elusive. This is largely owing to the fact that they are difficult to handle, being insoluble in aqueous media, and that no one gene alone determines their synthesis. The heterogeneity of the lipid moiety provides a further confounding factor. GSLs are central components within lipid rafts, which are major foci for transmembrane signaling and interactions between eukaryotic cells and microbial pathogens. GSL receptor function often requires the lipid moiety, and lipid-free sugar analogs are ineffective inhibitors. In order to overcome some of these problems, we have synthesized adamantyl GSL analogs which, in part, mimic GSL membrane receptor function in solution. These compounds are made by replacing the endogenous fatty acid with an adamantan frame. This rigid hydrophobic structure surprisingly increases the water solubility of the conjugate and retains receptor function. These GSL mimics provide probes to study GSL receptor function within cells. They compete with native GSLs for ligand binding and are taken up by cells to potentially alter GSL-mediated interaction. We are focused on two derivatives, adamantyl globotriaosyl ceramide and adamantyl sulfogalactosyl ceramide, and have used these analogs to probe GSL function in microbial pathology and hsp70 function. This chapter describes the syntheses and uses of these mimics.

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Author information

Authors and Affiliations

  1. Section of Infection, Immunity, Injury, and Repair, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada

    Clifford Lingwood PhD, Skanda Sadacharan PhD, Maan Abul-Milh PhD, Murugespillai Mylvaganum PhD & Marcus Peter PhD

  2. Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada

    Clifford Lingwood PhD

Authors
  1. Clifford Lingwood PhD
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  2. Skanda Sadacharan PhD
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  3. Maan Abul-Milh PhD
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  4. Murugespillai Mylvaganum PhD
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  5. Marcus Peter PhD
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Editor information

Editors and Affiliations

  1. Department of Medicine, Queen’s University, Kingston, Ontario, Canada

    Inka Brockhausen

  2. Department of Biochemistry, Queen’s University, Kingston, Ontario, Canada

    Inka Brockhausen

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© 2006 Humana Press Inc.

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Lingwood, C., Sadacharan, S., Abul-Milh, M., Mylvaganum, M., Peter, M. (2006). Soluble Adamantyl Glycosphingolipid Analogs as Probes of Glycosphingolipid Function. In: Brockhausen, I. (eds) Glycobiology Protocols. Methods in Molecular Biology, vol 347. Humana Press. https://doi.org/10.1385/1-59745-167-3:305

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  • DOI: https://doi.org/10.1385/1-59745-167-3:305

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-553-8

  • Online ISBN: 978-1-59745-167-3

  • eBook Packages: Springer Protocols

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