GM3, GM2 and GM1 mimics designed for biosensing: chemoenzymatic synthesis, target affinities and 900 MHz NMR analysis

A.V. Pukin, C.A.G.M. Weijers, B. van Lagen, R. Wechselberger, B. Sun, M. Gilbert, M.F. Karwaski, D.E.A. Florack, B.C. Jacobs, A.P. Tio-Gillen, A. van Belkum, H.P. Endtz, G.M. Visser, H. Zuilhof

Research output: Contribution to journalArticleAcademicpeer-review

34 Citations (Scopus)

Abstract

Undec-10-enyl, undec-10-ynyl and 11-azidoundecyl glycoside analogues corresponding to the oligosaccharides of human gangliosides GM3, GM2 and GM1 were synthesized in high yields using glycosyltransferases from Campylobacter jejuni. Due to poor water solubility of the substrates, the reactions were carried out in methanol¿water media, which for the first time were shown to be compatible with the C. jejuni ¿-(2¿3)-sialyltransferase (CST-06) and ß-(1¿4)-N-acetylgalactosaminyltransferase (CJL-30). Bioequivalence of our synthetic analogues and natural gangliosides was examined by binding to Vibrio cholerae toxin and to the B subunit of Escherichia coli heat-labile enterotoxin. This bioequivalence was confirmed by binding mouse and human monoclonal antibodies to GM1 and acute phase sera containing IgM and IgG antibodies to GM1 from patients with the immune-mediated polyneuropathy Guillain¿Barré syndrome. The synthesized compounds were analyzed by 1D and 2D 900 MHz NMR spectroscopy. TOCSY and DQF-COSY experiments in combination with 13C¿1H correlation measurements (HSQC, HMBC) were carried out for primary structural characterization, and a complete assignment of all 1H and 13C chemical shifts is presented.
Original languageEnglish
Pages (from-to)636-650
JournalCarbohydrate Research : an international journal
Volume343
Issue number4
DOIs
Publication statusPublished - 2008

Keywords

  • covalently attached monolayers
  • crystalline silicon surfaces
  • nuclear-magnetic-resonance
  • extremely mild attachment
  • heat-labile enterotoxin
  • one-pot synthesis
  • campylobacter-jejuni
  • cholera-toxin
  • solid-phase
  • guillain-barre

Fingerprint Dive into the research topics of 'GM3, GM2 and GM1 mimics designed for biosensing: chemoenzymatic synthesis, target affinities and 900 MHz NMR analysis'. Together they form a unique fingerprint.

Cite this