Chemoenzymatic Synthesis of Functional Sialyl LewisX Mimetics with a Heteroaromatic Core

Functional mimetics of the sialyl LewisX tetrasaccharide were prepared by the enzymatic sialylation of a 1,3‐diglycosylated indole and a glycosyl azide, which was subsequently transformed into a 1,4‐diglycosylated 1,2,3‐triazole, by using the trans‐sialidase of Trypanosoma cruzi. These compounds inh...

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Bibliographic Details
Published in:Chemistry, an Asian journal an Asian journal, 2014-08, Vol.9 (8), p.2119-2125
Main Authors: Schlemmer, Claudine, Wiebe, Christine, Ferenc, Dorota, Kowalczyk, Danuta, Wedepohl, Stefanie, Ziegelmüller, Patrick, Dernedde, Jens, Opatz, Till
Format: Article
Language:English
Subjects:
cell adhesion
Chemistry
enzyme catalysis
heterocycles
oligosaccharides
Protozoa
saccharide mimetics
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Summary:Functional mimetics of the sialyl LewisX tetrasaccharide were prepared by the enzymatic sialylation of a 1,3‐diglycosylated indole and a glycosyl azide, which was subsequently transformed into a 1,4‐diglycosylated 1,2,3‐triazole, by using the trans‐sialidase of Trypanosoma cruzi. These compounds inhibited the binding of E‐, L‐, and P‐selectin‐coated nanoparticles to polyacrylamide‐bound sialyl‐LewisX‐containing neighboring sulfated tyrosine residues (sTyr/sLeX‐PAA) at low or sub‐millimolar concentrations. Except for E‐selectin, the mimetics showed higher activities than the natural tetrasaccharide. X‐Men: Replacement of the GlcNAc residue within the well‐known natural cell‐adhesion molecule sialyl‐LewisX with 1,2,3‐triazole or indole moieties furnishes functional mimetics that show enhanced binding to P‐ and/or L‐selectin. The new ligands were prepared from short chemoenzymatic syntheses by using the trans‐sialidase of the human pathogen Trypanosoma cruzi.
ISSN:1861-4728
1861-471X
DOI:10.1002/asia.201402118