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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ABO Blood-Group System*
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Disaccharides / chemical synthesis*
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Disaccharides / metabolism
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Disaccharides / pharmacology
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Galactosyltransferases / antagonists & inhibitors*
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Humans
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Kinetics
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N-Acetylgalactosaminyltransferases / metabolism
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Uridine Diphosphate Galactose / metabolism*
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Xanthines / chemical synthesis*
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Xanthines / metabolism
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Xanthines / pharmacology
Substances
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9-(5-O-galactopyranosyl)arabinityl-1,3,7-trihydropurine-2,6,8-trione
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ABO Blood-Group System
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Disaccharides
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Enzyme Inhibitors
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Xanthines
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Uridine Diphosphate Galactose
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Galactosyltransferases
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N-Acetylgalactosaminyltransferases
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UDPgalactosamine-galactose acetylgalactosaminyltransferase
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blood-group-substance alpha-D-galactosyltransferase