Fragment-based development of triazole-substituted O-galactosyl aldoximes with fragment-induced affinity and selectivity for galectin-3

Org Biomol Chem. 2009 Oct 7;7(19):3982-90. doi: 10.1039/b909091f. Epub 2009 Jul 20.

Abstract

A fragment-based development of 3C-triazol-1-yl-O-galactopyranosyl aldoximes led to the discovery of highly selective and high affinity (K(d) down to 11 microm) small monosaccharide based inhibitors of galectin-3. Galectin-7, 8 N-terminal CRD, and 9 N-terminal CRD bound the inhibitors only weakly. The galectin-3 selectivity was hypothesized to stem from interaction of the aldoxime moiety with a site not present in the other galectins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Binding Sites
  • Drug Discovery
  • Galectin 3 / antagonists & inhibitors
  • Galectin 3 / chemistry
  • Galectin 3 / metabolism*
  • Hydroxylamines / chemistry
  • Models, Molecular
  • Molecular Conformation
  • Oxidation-Reduction
  • Oximes / chemical synthesis
  • Oximes / chemistry*
  • Oximes / metabolism*
  • Oximes / pharmacology
  • Protein Binding
  • Protein Structure, Tertiary
  • Substrate Specificity
  • Triazoles / chemistry*

Substances

  • Galectin 3
  • Hydroxylamines
  • Oximes
  • Triazoles