title: A nonionic inhibitor with high specificity for the UDP-Gal donor binding site of human blood group B galactosyltransferase: design, synthesis, and characterization.
abstract: 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.
authors: Organic Chemistry, Department of Chemistry, Faculty of Sciences, University of Hamburg, Martin Luther King Platz 6, 20146 Hamburg, Germany.
authors: Katrin
authors: K
authors: Schaefer
authors: Nora
authors: N
authors: Sindhuwinata
authors: Thomas
authors: T
authors: Hackl
authors: Miriam P
authors: MP
authors: Kötzler
authors: Felix C
authors: FC
authors: Niemeyer
authors: Monica M
authors: MM
authors: Palcic
authors: Thomas
authors: T
authors: Peters
authors: Bernd
authors: B
authors: Meyer
mesh_terms: D000017:ABO Blood-Group System; D004187:Disaccharides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005700:Galactosyltransferases / Q000037:antagonists & inhibitors*; D006801:Humans; D007700:Kinetics; D017350:N-Acetylgalactosaminyltransferases / Q000378:metabolism; D014531:Uridine Diphosphate Galactose / Q000378:metabolism*; D014970:Xanthines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
chemical_list: C581011:9-(5-O-galactopyranosyl)arabinityl-1,3,7-trihydropurine-2,6,8-trione; D000017:ABO Blood-Group System; D004187:Disaccharides; D004791:Enzyme Inhibitors; D014970:Xanthines; D014531:Uridine Diphosphate Galactose; D005700:Galactosyltransferases; D017350:N-Acetylgalactosaminyltransferases; C003742:UDPgalactosamine-galactose acetylgalactosaminyltransferase; C023155:blood-group-substance alpha-D-galactosyltransferase