Chemoenzymatic synthesis of functional sialyl lewis(x) mimetics with a heteroaromatic core
C. Schlemmer, C. Wiebe, D. Ferenc, D. Kowalczyk, S. Wedepohl, P. Ziegelmüller, J. Dernedde, T. Opatz – 2014
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.