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

Bioorganic & Medicinal Chemistry
Alexander TitzBeat Ernst

Abstract

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.

References

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Sep 12, 2007·Bioorganic & Medicinal Chemistry·Alexander TitzBeat Ernst
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Citations

Jan 23, 2016·Chemical Reviews·Vinod K TiwariXi Chen
May 16, 2015·Bioorganic & Medicinal Chemistry·Marcelo Fiori MarchioriVanessa Leiria Campo
Jun 4, 2014·Chemistry, an Asian Journal·Claudine SchlemmerTill Opatz
Mar 3, 2012·Experimental Dermatology·Taís GratieriYogeshvar N Kalia
Jun 25, 2021·Chemical Reviews·Anand K AgrahariVinod K Tiwari

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