Protein subtype-targeting through ligand epimerization: talose-selectivity of galectin-4 and galectin-8

Bioorg Med Chem Lett. 2008 Jul 1;18(13):3691-4. doi: 10.1016/j.bmcl.2008.05.066. Epub 2008 May 20.

Abstract

A series of O2 and O3-derivatized methyl beta-d-talopyranosides were synthesized and evaluated in vitro as inhibitors of the galactose-binding galectin-1, -2, -3, -4 (N- and C-terminal domains), 8 (N-terminal domain), and 9 (N-terminal domain). Galectin-4C and 8N were found to prefer the d-talopyranose configuration to the natural ligand d-galactopyranose configuration. Derivatization at talose O2 and/or O3 provided selective submillimolar inhibitors for these two galectins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoates / chemistry*
  • Binding Sites
  • Galactose / chemistry
  • Galectin 1 / chemistry
  • Galectin 3 / chemistry
  • Galectin 4 / chemistry*
  • Galectins / chemistry*
  • Glycosides / chemistry*
  • Humans
  • Lactones / chemistry*
  • Ligands
  • Models, Chemical
  • Protein Engineering / methods
  • Protein Structure, Tertiary
  • Pyrans / chemistry
  • Spectrometry, Fluorescence / methods

Substances

  • Benzoates
  • Galectin 1
  • Galectin 3
  • Galectin 4
  • Galectins
  • Glycosides
  • L-talo-gamma-lactone
  • LGALS8 protein, human
  • LGALS9 protein, human
  • Lactones
  • Ligands
  • Pyrans
  • methyl 2-O-acetyl-3-O-toluoyltalopyranoside
  • Galactose