Tuning the preference of thiodigalactoside- and lactosamine-based ligands to galectin-3 over galectin-1

J Med Chem. 2013 Feb 14;56(3):1350-4. doi: 10.1021/jm301677r. Epub 2013 Jan 23.

Abstract

Inhibitors for galectin-1 and -3 were synthesized from thiodigalactoside and lactosamine by derivatization of the galactose C3. Introduction of 4-phenyl-1H-1,2,3-triazol-1-yl substituents at the thiodigalactoside C3 by CuAAC, targeting arginine-arene interactions, increased the affinity to 13 nM but yielded little selectivity. The bulkier 4-(4-phenoxyphenyl)-1H-1,2,3-triazol-1-yl substituent, however, increased the preference for galectin-3 over galectin-1 to more than 200-fold. Modeling showed more arginine-arene interactions for galectin-3 than for galectin-1. Introducing 4-phenoxyaryl groups on lactosamine had a similar effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Sugars / chemistry*
  • Galectin 1 / chemistry*
  • Galectin 3 / chemistry*
  • Ligands
  • Mass Spectrometry
  • Molecular Structure
  • Thiogalactosides / chemistry*

Substances

  • Amino Sugars
  • Galectin 1
  • Galectin 3
  • Ligands
  • Thiogalactosides
  • lactosamine
  • thiodigalactoside