New sialyl Lewis(x) mimic containing an alpha-substituted beta(3)-amino acid spacer

Carbohydr Res. 2008 Jan 14;343(1):31-8. doi: 10.1016/j.carres.2007.10.001. Epub 2007 Oct 7.

Abstract

A highly convergent and efficient synthesis of a new sialyl Lewis(x) (sLe(x)) mimic, which was predicted by computational studies to fulfil the spacial requirements for a selectin antagonist, has been developed. With a beta(2,3)-amino acid residue l-galactose (bioisostere of the l-fucose moiety present in the natural sLe(x)) and succinate are linked, leading to a mimic of sLe(x) that contains all the required pharmacophores, namely the 3- and 4-hydroxy group of l-fucose, the 4- and 6-hydroxy group of d-galactose and the carboxylic acid of N-acetylneuraminic acid. The key step of the synthesis involves a tandem reaction consisting of a N-deprotection and a suitable O-->N intramolecular acyl migration reaction which is promoted by cerium ammonium nitrate (CAN). Finally, the new sialyl Lewis(x) mimic was biologically evaluated in a competitive binding assay.

MeSH terms

  • Amino Acids / chemistry*
  • Binding, Competitive
  • Cross-Linking Reagents
  • Molecular Mimicry*
  • Oligosaccharides / chemistry*
  • Sialyl Lewis X Antigen

Substances

  • Amino Acids
  • Cross-Linking Reagents
  • Oligosaccharides
  • Sialyl Lewis X Antigen