Mannose glycoconjugates functionalized at positions 1 and 6. Binding analysis to DC-SIGN using biosensors

Bioconjug Chem. 2007 May-Jun;18(3):963-9. doi: 10.1021/bc060369z. Epub 2007 Mar 10.

Abstract

The design of glycoconjugates to allow the generation of multivalent ligands capable of interacting with the receptor DC-SIGN is a topic of high interest due to the role played by this lectin in pathogen infections. Mannose, a ligand of this lectin, could be conjugated at two different positions, 1 and 6, not implicated in the binding process. We have prepared mannose conjugates at these two positions with a long spacer to allow their attachment to a biosensor chip surface. Analysis of the interaction between these surfaces and the tetravalent extracellular domain (ECD) of DC-SIGN by SPR biosensor has demonstrated that both positions are available for this conjugation without affecting the protein binding process. These results emphasize the possibility to conjugate mannose at position 6, allowing the incorporation of hydrophobic groups at the anomeric position to interact with hydrophobic residues in the carbohydrate recognition domain of DC-SIGN, increasing binding affinities. This fact is relevant for the future design of new ligands and the corresponding multivalent systems for DC-SIGN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biosensing Techniques*
  • Cell Adhesion Molecules / chemistry*
  • Glycoconjugates / chemical synthesis
  • Glycoconjugates / chemistry
  • Humans
  • Lectins, C-Type / chemistry*
  • Maltose / analogs & derivatives*
  • Maltose / chemical synthesis
  • Maltose / chemistry
  • Mannose / chemistry*
  • Receptors, Cell Surface / chemistry*
  • Surface Plasmon Resonance

Substances

  • 2-((13-amino-4,7,10-trioxatridecylamino)succinamido)ethyl maltopyranoside
  • 6-O-(2-((13-amino-4,7,10-trioxatridecylamino)succinamido)ethyl)maltopyranose
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Glycoconjugates
  • Lectins, C-Type
  • Receptors, Cell Surface
  • Maltose
  • Mannose