Rational design of novel glycomimetics: inhibitors of concanavalin A

Bioorg Med Chem Lett. 2008 Dec 15;18(24):6573-5. doi: 10.1016/j.bmcl.2008.09.095. Epub 2008 Oct 1.

Abstract

A virtual screening approach was used to identify new glycomimetics. The National Cancer Institute Diversity Set was docked into the carbohydrate binding site of the lectin concanavalin A (ConA). The resulting poses were analyzed and 19 molecules were tested for inhibition with an enzyme-linked lectin assay (ELLA). Eight of the 19 molecules inhibited ConA-carbohydrate binding. The two most potent inhibitors have IC(50) values that are an order of magnitude smaller than the monosaccharide methyl alpha-D-mannopyranoside.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Binding Sites
  • Carbohydrate Conformation
  • Catalytic Domain
  • Chemistry, Pharmaceutical / methods*
  • Concanavalin A / chemical synthesis*
  • Concanavalin A / chemistry
  • Concanavalin A / pharmacology*
  • Crystallography, X-Ray / methods
  • Drug Design
  • Fabaceae / metabolism
  • Inhibitory Concentration 50
  • Lectins / chemistry
  • Methylmannosides / chemistry
  • Models, Chemical
  • Molecular Conformation
  • Protein Binding

Substances

  • Lectins
  • Methylmannosides
  • Concanavalin A
  • methylmannoside