Arginine binding motifs: design and synthesis of galactose-derived arginine tweezers as galectin-3 inhibitors

J Med Chem. 2008 Apr 10;51(7):2297-301. doi: 10.1021/jm701266y. Epub 2008 Mar 5.

Abstract

Anionic O2 derivatives of methyl 3-deoxy-3-(4-methylbenzamido)-1-thio-beta-D-galactopyranoside have been synthesized as inhibitors against galectin-3. The sulfate, H-phosphonate, and benzyl phosphate derivatives showed an increased affinity as compared to the parent unsubstituted galactopyranoside. Modeling revealed arginine-144 being pinched by the C3 benzamide and O2 anionic substituents in that the benzamide stacked face-to-face and the anionic O2 substituent ion-paired with the guanidinium moiety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine* / analogs & derivatives
  • Arginine* / chemical synthesis
  • Arginine* / pharmacology
  • Benzamides / chemical synthesis*
  • Benzamides / chemistry
  • Benzamides / pharmacology*
  • Binding Sites
  • Binding, Competitive
  • Drug Design
  • Galactose / chemistry*
  • Galactosides / chemical synthesis*
  • Galactosides / chemistry
  • Galactosides / pharmacology*
  • Galectin 3 / antagonists & inhibitors*
  • Models, Molecular
  • Molecular Conformation
  • Oxygen / chemistry
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Benzamides
  • Galactosides
  • Galectin 3
  • Arginine
  • Oxygen
  • Galactose