Enzymatic Synthesis of Tumor-Associated Carbohydrate Antigen Globo-H Hexasaccharide

We report the enzymatic synthesis of an important tumor-associated carbohydrate antigen, Globo-H hexasaccharide. Starting with Lac-OBn as the initial acceptor, this approach employs three glycosyltransferases: LgtC, an alpha1,4-galactosyltransferase; LgtD, a bifunctional beta1,3-galactosyl/beta1,3-N-acetylgalactosaminyltransferase; and WbsJ, an alpha1,2-fucosyltransferase. In addition, two epimerases, GalE and WbgU, were also employed for the generation of more expensive sugar nucleotides, UDP-Gal and UDP-GalNAc, from their corresponding inexpensive C4 epimers. This study represents a facile enzymatic synthesis of the Globo-H antigen.