Organic Chemistry, Department of Chemistry, Faculty of Sciences, University of Hamburg, Martin Luther King Platz 6, 20146 Hamburg, Germany.
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.
9-(5-O-α-D-半乳糖吡喃糖苷基)-D-阿拉伯糖基-1,3,7-三羟基嘌呤-2,6,8-三酮（1）被设计并合成作为人血型 B 半乳糖基转移酶（GTB）供体结合部位的非离子型抑制剂。酶学特征表明 1 非常特异，因为高度同源的人 N-乙酰半乳糖胺基转移酶（GTA）不受抑制。1 的结合表位显示阿拉伯糖连接基高度参与，而半乳糖残基仅通过其 C-2 位点与蛋白质接触，这对于区分 GTA 转移的半乳糖和 N-乙酰半乳糖胺非常重要。该方法可以产生高度特异的糖基转移酶抑制剂。
