Insights into molecular recognition of Lewis(X) mimics by DC-SIGN using NMR and molecular modelling

Cinzia Guzzi, Jesús Angulo, Fabio Doro, José J Reina, Michel Thépaut, Franck Fieschi, Anna Bernardi, Javier Rojo, Pedro M Nieto

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

In this work, we have studied in detail the binding of two a-fucosylamide-based mimics of Lewis(X) to DC-SIGN ECD (ECD = extracellular domain) using STD NMR and docking. We have concluded that the binding mode occurs mainly through the fucose moiety, in the same way as Lewis(X). Similarly to other mimics containing mannose or fucose previously studied, we have shown that both compounds bind to DC-SIGN ECD in a multimodal fashion. In this case, the main contact is the interaction of two hydroxyl groups one equatorial and the other one axial (O3 and O4) of the fucose with the Ca(2+) as Lewis(X) and similarly to mannose-containing mimics (in this case the interacting groups are both in the equatorial position). Finally, we have measured the K(D) of one mimic that was 0.4 mM. Competitive STD NMR experiments indicate that the aromatic moiety provides additional binding contacts that increase the affinity.
Original languageEnglish
Pages (from-to)7705-7712
Number of pages8
JournalOrganic & Biomolecular Chemistry
Volume9
Issue number22
DOIs
Publication statusPublished - 26 Oct 2011

Keywords

  • Dendritic Cells
  • Models, Molecular
  • Humans
  • Mannose
  • Fucose
  • Biomimetics
  • Immunity, Innate
  • Antigens, CD15
  • Receptors, Cell Surface
  • Protein Binding
  • Cell Adhesion Molecules
  • Binding Sites
  • Magnetic Resonance Spectroscopy
  • Small Molecule Libraries
  • Lectins, C-Type
  • Kinetics
  • Molecular Sequence Data
  • Molecular Mimicry
  • Protein Structure, Tertiary
  • Carbohydrate Conformation

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