Sialyl Lewis(x) analogs based on a quinic acid scaffold as the fucose mimic

Bioorg Med Chem Lett. 2005 Jul 1;15(13):3224-8. doi: 10.1016/j.bmcl.2005.05.004.

Abstract

(-)-Quinic acid was used as a starting material for the preparation of sialyl Lewis(x) mimetics in order to target E-selectin. Spatial orientation of the hydroxyl groups of quinic acid could mimic the l-fucose ones. Introduction of a side chain ending with a carboxylic acid was effected to replace the sialic acid interaction at the carbohydrate recognition domain. A first series of derivatives, incorporating amino acids linked to quinic acid, were tested for their affinity and found to interact with E-selectin with IC(50) within the millimolar range.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / drug effects
  • E-Selectin / drug effects*
  • E-Selectin / metabolism
  • Fucose / chemistry
  • HL-60 Cells
  • Humans
  • Inhibitory Concentration 50
  • Ligands
  • Molecular Mimicry
  • Oligosaccharides / chemical synthesis*
  • Oligosaccharides / metabolism
  • Oligosaccharides / pharmacology
  • P-Selectin / drug effects
  • Quinic Acid / chemical synthesis*
  • Quinic Acid / pharmacology
  • Sialyl Lewis X Antigen

Substances

  • E-Selectin
  • Ligands
  • Oligosaccharides
  • P-Selectin
  • Sialyl Lewis X Antigen
  • Quinic Acid
  • Fucose