1211463-85-2Relevant academic research and scientific papers
Probing the carbohydrate recognition domain of E-selectin: The importance of the acid orientation in sLex mimetics
Titz, Alexander,Patton, John,Smiesko, Martin,Radic, Zorana,Schwardt, Oliver,Magnani, John L.,Ernst, Beat
experimental part, p. 19 - 27 (2010/03/30)
The selectin-leukocyte interaction is the initial event in the early inflammatory cascade. This interplay proceeds via the terminal tetrasaccharide sialyl Lewisx (sLex), 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 sLex as lead structure, containing the essential pharmacophores pre-oriented in the bioactive conformation. In this work, we describe a set of competitive sLex 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.
