Synthesis and conformational analysis of a conformationally constrained trisaccharide, and complexation properties with concanavalin A

Nathalie Navarre, Nicolas Amiot, Anita Van Oijen, Anne Imberty, Ana Poveda, Jesus Jiménez-Barbero, Alan Cooper, Margaret A. Nutley, Geert Jan Boons*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The trisaccharide β-D-GlcNAc(1→2)α-D-Man(1→3)D-Man is a fragment of a biantennary glycan that is recognized byα-D-Man-specific lectins such as concanavalin A (ConA), Lathyrus ochrus lectin, lentil lectin, and can adopt several conformations upon binding. To probe the importance of loss of flexibility of a saccharide during binding with ConA this trisaccharide has been synthesized in a conformationally constrained form where a methylene acetal bridge mimics a GlcNAc-O-6″⋯Man-O-4 intramolecular hydrogen bond. Microcalorimetry measurements revealed that the conformationally constrained compound has a more favorable entropy term but this term is offset by a smaller enthalpy term. NMR spectroscopic studies have shown that the cyclic compound is indeed considerably less flexible than the linear compound and both compounds adopt mainly one conformation. SYBYL software together with energy parameters appropriate for carbohydrates was used for a systematic conformational search. The linear compound is very flexible. A clustering method determined seven main conformational families. Six possible conformational families were identified for the cyclic compound when considering the orientations of the βGlcNAc(1→2)Man and αβMan-(1→3)Man glycosidic bonds. The central mannose residue was docked in the binding site of ConA and the complex was refined. The results are compared with crystal structures of legume lectin-oligosaccharide complexes and with the NMR and thermodynamic data.

Original languageEnglish
Pages (from-to)2281-2294
Number of pages14
JournalChemistry - A European Journal
Volume5
Issue number8
DOIs
Publication statusPublished - 1 Jan 1999
Externally publishedYes

Keywords

  • Calorimetry
  • Carbohydrates
  • Lectins
  • Molecular modeling
  • Olisaccharides

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