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

作者：Schaefer Katrin; Sindhuwinata Nora; Hackl Thomas; Koetzler Miriam P; Niemeyer Felix C; Palcic Monica M; Peters Thomas; Meyer Bernd^*

来源：Journal of Medicinal Chemistry, 2013, 56(5): 2150-2154.

DOI：10.1021/jm300642a

9-(5-O-alpha-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.

• 出版日期2013-3-14