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Synthesis of Glycosaminoglycan Mimetics Through Sulfation of Polyphenols

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Glycosaminoglycans

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

Abstract

In nearly all cases of biological activity of sulfated GAGs, the sulfate group(s) are critical for interacting with target proteins. A growing paradigm is that appropriate small, sulfated, nonsaccharide GAG mimetics can be designed to either mimic or interfere with the biological functions of natural GAG sequences resulting in the discovery of either antagonist or agonist agents. A number of times these sulfated NSGMs can be computationally designed based on the parent GAG–protein interaction. The small sulfated NSGMs may possess considerable aromatic character so as to engineer hydrophobic, hydrogen-bonding, Coulombic or cation–pi forces in their interactions with target protein(s) resulting in higher specificity of action relative to parent GAGs. The sulfated NSGMs can be easily synthesized in one step from appropriate natural polyphenols through chemical sulfation under microwave-based conditions. We describe step-by-step procedures to perform microwave-based sulfation of several small polyphenol scaffolds so as to prepare homogenous NSGMs containing one to more than 10 sulfate groups per molecule in high yields.

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, 800 E. Leigh Street, Suite 212, Richmond, VA, 23219, USA

    Rami A. Al-Horani, Rajesh Karuturi, Stephen Verespy III & Umesh R. Desai

  2. Chemical Biology Program, Department of Chemistry, Virginia Commonwealth University, Richmond, VA, 23219, USA

    Stephen Verespy III

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  1. Rami A. Al-Horani
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  2. Rajesh Karuturi
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  3. Stephen Verespy III
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  4. Umesh R. Desai
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Correspondence to Umesh R. Desai .

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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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Al-Horani, R.A., Karuturi, R., Verespy, S., Desai, U.R. (2015). Synthesis of Glycosaminoglycan Mimetics Through Sulfation of Polyphenols. 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_7

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  • DOI: https://doi.org/10.1007/978-1-4939-1714-3_7

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1713-6

  • Online ISBN: 978-1-4939-1714-3

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