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A Single Route to Mammalian N‐Glycans Substituted with Core Fucose and Bisecting GlcNAc
Author(s) -
Luber Thomas,
Niemietz Mathäus,
Karagiannis Theodoros,
Mönnich Manuel,
Ott Dimitri,
Perkams Lukas,
Walcher Janika,
Berger Lukas,
Pischl Matthias,
Weishaupt Markus,
Eller Steffen,
Hoffman Joanna,
Unverzagt Carlo
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201807742
Subject(s) - fucosylation , glycan , fucose , antibody dependent cell mediated cytotoxicity , chemistry , glycoprotein , glycosylation , biochemistry , carbohydrate conformation , protecting group , enzyme , cytotoxicity , stereochemistry , fucosyltransferase , antibody , combinatorial chemistry , polysaccharide , organic chemistry , biology , in vitro , immunology , alkyl
The occurrence of α1,6‐linked core fucose on the N‐glycans of mammalian glycoproteins is involved in tumor progression and reduces the bioactivity of antibodies in antibody‐dependent cell‐mediated cytotoxicity (ADCC). Since core‐fucosylated N‐glycans are difficult to isolate from natural sources, only chemical or enzymatic synthesis can provide the desired compounds for biological studies. A general drawback of chemical α‐fucosylation is that the chemical assembly of α1,6‐linked fucosides is not stereospecific. A robust and general method for the α‐selective fucosylation of acceptors with primary hydroxy groups in α/β ratios exceeding 99:1 was developed. The high selectivities result from the interplay of an optimized protecting group pattern of the fucosyl donors in combination with the activation principle and the reaction conditions. Selective deprotection yielded versatile azides of all mammalian complex‐type core‐fucosylated N‐glycans with 2‐4 antennae and optional bisecting GlcNAc.