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Synthesis of Selective Inhibitors of Heparan Sulfate and Chondroitin Sulfate Proteoglycan Biosynthesis

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Glycosaminoglycans

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1229))

Abstract

Glycosaminoglycan (GAG) side chains of proteoglycans are involved in a wide variety of developmental and pathophysiological functions. Similar to a gene knockout, the ability to inhibit GAG biosynthesis would allow us to examine the function of endogenous GAG chains. However, ubiquitously and irreversibly knocking out all GAG biosynthesis would cause multiple effects making it difficult to attribute a specific biological role to a specific GAG structure in spatiotemporal manner. Reversible and selective inhibition of GAG biosynthesis would allow us to examine the importance of endogenous GAGs to specific cellular, tissue, or organ systems. In this chapter, we describe the chemical synthesis and biological evaluation of 4-deoxy-4-fluoro-xylosides as selective inhibitors of heparan sulfate and chondroitin/dermatan sulfate proteoglycan biosynthesis.

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Acknowledgement

This work was supported in part by NIH grants (GM075168 and HL107152 to B.K.), Human Frontier Science Program grant (RGP0044/2006 to B.K.), and KAKENHI grant (No. 23590005 to M.K.).

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Authors and Affiliations

  1. Interdepartmental Program in Neuroscience, University of Utah, Salt lake City, UT, USA

    Caitlin Mencio & Balagurunathan Kuberan

  2. Department of Chemistry, Sir Parashurambhau College, Pune, India

    Dinesh R. Garud

  3. Department of Medicinal Chemistry, University of Utah, Salt lake City, UT, USA

    Balagurunathan Kuberan

  4. Department of Bioengineering, University of Utah, Salt lake City, UT, USA

    Balagurunathan Kuberan

  5. Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan

    Mamoru Koketsu

Authors
  1. Caitlin Mencio
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  2. Dinesh R. Garud
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  3. Balagurunathan Kuberan
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  4. Mamoru Koketsu
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Corresponding author

Correspondence to Mamoru Koketsu .

Editor information

Editors and Affiliations

  1. Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah, USA

    Kuberan Balagurunathan

  2. Department of Genetics, Cell Biology and Development, The University of Minnesota, Minneapolis, Minnesota, USA

    Hiroshi Nakato

  3. Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia, USA

    Umesh R. Desai

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Mencio, C., Garud, D.R., Kuberan, B., Koketsu, M. (2015). Synthesis of Selective Inhibitors of Heparan Sulfate and Chondroitin Sulfate Proteoglycan Biosynthesis. In: Balagurunathan, K., Nakato, H., Desai, U. (eds) Glycosaminoglycans. Methods in Molecular Biology, vol 1229. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1714-3_8

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  • DOI: https://doi.org/10.1007/978-1-4939-1714-3_8

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1713-6

  • Online ISBN: 978-1-4939-1714-3

  • eBook Packages: Springer Protocols

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