The design and synthesis of a selective inhibitor of fucosyltransferase VI
Carmen Galan, M.; Venot, Andre P.; Phillips, Robert S.; Boons, Geert-Jan; Carmen Galan M.; Complex Carbohydrate Research Center, University of Georgia; Venot Andre P.; Complex Carbohydrate Research Center, University of Georgia; Phillips Robert S.; Department of Chemistry, University of Georgia; Boons Geert-Jan; Complex Carbohydrate Research Center, University of Georgia; Department of Chemistry, University of Georgia
Журнал:
Organic & Biomolecular Chemistry
Дата:
2004
Аннотация:
Inversion of configuration of the C-2⠲ hydroxyl of methyl N-acetyllactosamine was accomplished by a two-step procedure involving oxidation to a ketone followed by reduction with NaBH4. After deprotection, the resulting derivative 2 was examined as a substrate for α-(2,6)- and α-(2,3)-sialyltransferase and fucosyltransferase III, IV, V and VI. It was found that none of these enzymes could glycosylate 2. However, it showed exquisite selectivity for inhibition of fucosyltransferase VI. The kinetic data support an unusual mechanism in which the inhibitor can bind to the GDP-fucose complex as well as another enzyme form.
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