A nonionic inhibitor with high specificity for the UDP-Gal donor binding site of human blood group B galactosyltransferase: design, synthesis, and characterization

J Med Chem. 2013 Mar 14;56(5):2150-4. doi: 10.1021/jm300642a. Epub 2013 Feb 28.


9-(5-O-α-D-galactopyranosyl)-D-arabinityl-1,3,7-trihydropurine-2,6,8-trione (1) was designed and synthesized as a nonionic inhibitor for the donor binding site of human blood group B galactosyltransferase (GTB). Enzymatic characterization showed 1 to be extremely specific, as the highly homologous human N-acetylgalactosaminyltransferase (GTA) is not inhibited. The binding epitope of 1 demonstrates a high involvement of the arabinityl linker, whereas the galactose residue is only making contact to the protein via its C-2 site, which is very important for the discrimination between galactose and N-acetylgalactosamine, the substrate transferred by GTA. The approach can generate highly specific glycosyltransferase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ABO Blood-Group System*
  • Disaccharides / chemical synthesis*
  • Disaccharides / metabolism
  • Disaccharides / pharmacology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Galactosyltransferases / antagonists & inhibitors*
  • Humans
  • Kinetics
  • N-Acetylgalactosaminyltransferases / metabolism
  • Uridine Diphosphate Galactose / metabolism*
  • Xanthines / chemical synthesis*
  • Xanthines / metabolism
  • Xanthines / pharmacology


  • 9-(5-O-galactopyranosyl)arabinityl-1,3,7-trihydropurine-2,6,8-trione
  • ABO Blood-Group System
  • Disaccharides
  • Enzyme Inhibitors
  • Xanthines
  • Uridine Diphosphate Galactose
  • Galactosyltransferases
  • N-Acetylgalactosaminyltransferases
  • UDPgalactosamine-galactose acetylgalactosaminyltransferase
  • blood-group-substance alpha-D-galactosyltransferase