title: Construction of a high-mannose-type glycan library by a renewed top-down chemo-enzymatic approach.
abstract: 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.
authors.affiliation: ERATO Science and Technology Agency (JST), Ito Glycotrilogy Project, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan), Fax: (+81) 48-462-4680.
authors.forename: Kohki
authors.initials: K
authors.lastname: Fujikawa
authors.forename: Akihiko
authors.initials: A
authors.lastname: Koizumi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hachisu
authors.forename: Akira
authors.initials: A
authors.lastname: Seko
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takeda
authors.forename: Yukishige
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry*; D006026:Glycoside Hydrolases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008358:Mannose / Q000737:chemistry*; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry* / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry*
chemical_list: D011134:Polysaccharides; D017351:N-Acetylglucosaminyltransferases; D006026:Glycoside Hydrolases; D008358:Mannose; D000117:Acetylglucosamine
keywords: carbohydrates; chemo-enzymatic synthesis; high-mannose-type glycans; posttranslational modifications; proteins