4.6 Article

Construction of a High-Mannose-Type Glycan Library by a Renewed Top-Down Chemo-Enzymatic Approach

Journal

CHEMISTRY-A EUROPEAN JOURNAL
Volume 21, Issue 8, Pages 3224-3233

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201405781

Keywords

carbohydrates; chemo-enzymatic synthesis; high-mannose-type glycans; posttranslational modifications; proteins

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A comprehensive method for the construction of a high-mannose-type glycan library by systematic chemo-enzymatic trimming of a single Man9-based precursor was developed. It consists of the chemical synthesis of a non-natural tridecasaccharide precursor, the orthogonal demasking of the non-reducing ends, and trimming by glycosidases, which enabled a comprehensive synthesis of high-mannose-type glycans in their mono-or non-glucosylated forms. It employed glucose, isopropylidene, and N-acetylglucosamine groups for blocking the A-, B-, and C-arms, respectively. After systematic trimming of the precursor, thirty-seven high-mannose-type glycans were obtained. The power of the methodology was demonstrated by the enzymatic activity of human recombinant N-acetylglucosaminyltransferase-I toward M7-M3 glycans, clarifying the substrate specificity in the context of high-mannose-type glycans.

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