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SIGLEC-4 (MAG) Antagonists: From the Natural Carbohydrate Epitope to Glycomimetics

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SialoGlyco Chemistry and Biology II

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 367))

Abstract

Siglec-4, also known as myelin-associated glycoprotein (MAG), is a member of the siglec (sialic acid-binding immunoglobulin-like lectins) family. MAG binds with high preference to sialic acids α(2–3)-linked to D-galactose. Although the involvement and relevance of its sialic acid binding activity is still controversial, it could be demonstrated that interactions of MAG with sialylated gangliosides play an important role in axon stability and regeneration. In this article we describe in detail our current understanding of the biological role and the carbohydrate specificity of siglec-4. Furthermore, this review compiles the intensive research efforts leading from the identification of the minimal oligosaccharide binding epitope in gangliosides via micromolar oligosaccharide mimics to the development of small molecular weight and more drug-like sialic acid derivatives binding with low nanomolar affinities. Such compounds will be useful to elucidate MAG’s biological functions, which are currently not fully understood.

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Notes

  1. 1.

    The numbering of the amino acids was carried out according to [69]; see also Swiss-Prot entry P20916.

  2. 2.

    For recent reviews, see [97–99].

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Authors and Affiliations

  1. Institute of Molecular Pharmacy, Pharmacenter, University of Basel, Klingelbergstrasse 50, CH-4056, Basel, Switzerland

    Oliver Schwardt & Beat Ernst

  2. Institute for Physiological Biochemistry, University Bremen, D-28334, Bremen, Germany

    Soerge Kelm

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  1. Oliver Schwardt
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  2. Soerge Kelm
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Correspondence to Beat Ernst .

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Editors and Affiliations

  1. Institute for Cellular Chemistry, Hannover, Germany

    Rita Gerardy-Schahn

  2. Lille University of Science and Technology, Villeneuve d'Ascq Cedex, France

    Philippe Delannoy

  3. Institute for Glycomics, Griffith University, Southport, Queensland, Australia

    Mark von Itzstein

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Schwardt, O., Kelm, S., Ernst, B. (2013). SIGLEC-4 (MAG) Antagonists: From the Natural Carbohydrate Epitope to Glycomimetics. In: Gerardy-Schahn, R., Delannoy, P., von Itzstein, M. (eds) SialoGlyco Chemistry and Biology II. Topics in Current Chemistry, vol 367. Springer, Cham. https://doi.org/10.1007/128_2013_498

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