Chemoenzymatic synthesis of functional sialyl Lewis(x) mimetics with a heteroaromatic core

Chem Asian J. 2014 Aug;9(8):2119-25. doi: 10.1002/asia.201402118. Epub 2014 May 30.

Abstract

Functional mimetics of the sialyl Lewis(X) 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-Lewis(X) -containing neighboring sulfated tyrosine residues (sTyr/sLe(X) -PAA) at low or sub-millimolar concentrations. Except for E-selectin, the mimetics showed higher activities than the natural tetrasaccharide.

Keywords: cell adhesion; enzyme catalysis; heterocycles; oligosaccharides; saccharide mimetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbohydrate Sequence
  • Carbon-13 Magnetic Resonance Spectroscopy
  • Glycoproteins / chemistry*
  • Molecular Mimicry*
  • Molecular Sequence Data
  • Neuraminidase / chemistry*
  • Oligosaccharides / chemistry*
  • Proton Magnetic Resonance Spectroscopy
  • Selectins / chemistry
  • Sialyl Lewis X Antigen
  • Spectrometry, Mass, Electrospray Ionization
  • Trypanosoma cruzi / enzymology

Substances

  • Glycoproteins
  • Oligosaccharides
  • Selectins
  • Sialyl Lewis X Antigen
  • trans-sialidase
  • Neuraminidase