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Probing the carbohydrate recognition domain of E-selectin: the importance of the acid orientation in sLex mimetics.
Journal article

Probing the carbohydrate recognition domain of E-selectin: the importance of the acid orientation in sLex mimetics.

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  • 2009-12-02
Published in:
  • Bioorganic & medicinal chemistry. - 2010
Binding Sites
Biomimetics
E-Selectin
Humans
Ligands
Models, Molecular
Oligosaccharides
Protein Binding
Serine
Sialyl Lewis X Antigen
English The selectin-leukocyte interaction is the initial event in the early inflammatory cascade. This interplay proceeds via the terminal tetrasaccharide sialyl Lewis(x) (sLe(x)), present on physiological selectin ligands and E- and P-selectins located on the endothelial surface. Blocking this process is regarded as a promising therapeutic approach for inflammatory diseases where excessive leukocyte efflux is responsible for tissue damage. Selectin antagonists are generally based on sLe(x) as lead structure, containing the essential pharmacophores pre-oriented in the bioactive conformation. In this work, we describe a set of competitive sLe(x) mimetics possessing the carboxylic acid pharmacophore equipped with additional hydrophobic substituents as neuraminic acid (Neu5Ac) replacements. This small library of antagonists derived from Huisgen-1,3-dipolar cycloadditions allows to further probe the carbohydrate recognition domain of E-selectin.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/143305
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