A Nonionic Inhibitor with High Specificity for the UDP-Gal Donor Binding Site of Human Blood Group B Galactosyltransferase: Design, Synthesis, and Characterization

9-(5-<i>O</i>-α-d-Galactopyranosyl)-d-arabinityl-1,3,7-trihydropurine-2,6,8-trione (<b>1</b>) was designed and synthesized as a nonionic inhibitor for the donor binding site of human blood group B galactosyltransferase (GTB). Enzymatic characterization showed <b>1</b> to be extremely specific, as the highly homologous human <i>N</i>-acetylgalactosaminyltransferase (GTA) is not inhibited. The binding epitope of <b>1</b> 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 <i>N</i>-acetylgalactosamine, the substrate transferred by GTA. The approach can generate highly specific glycosyltransferase inhibitors