A Glycosyltransferase Inhibitor from a Molecular Fragment Library Simultaneously Interferes with Metal Ion and Substrate Binding

A fragmented approach: 3-Phenyl-5-piperazino-1,2,4-thiadiazole (designated “compound 382” in the Ro5 Maybridge Fragment Library, see scheme) is demonstrated to be an effective inhibitor of human blood group glycosyltransferase B. The compound interferes with both acceptor and donor binding and also displaces the Mn2+ ion in the binding pocket.