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Title: Glycosylation engineering of therapeutic IgG antibodies: challenges for the safety, functionality and efficacy
Authors: Mimura, Yusuke
Katoh, Toshihiko  kyouindb  KAKEN_id
Saldova, Radka
O’Flaherty, Roisin
Izumi, Tomonori
Mimura-Kimura, Yuka
Utsunomiya, Toshiaki
Mizukami, Yoichi
Yamamoto, Kenji
Matsumoto, Tsuneo
Rudd, Pauline M.
Author's alias: 加藤, 紀彦
Keywords: chemoenzymatic glycoengineering
crystal structure
glycosylation intravenous immunoglobulin
sialic acid
ultra performance liquid chromatography
Issue Date: Jan-2018
Publisher: Springer Nature
Journal title: Protein & Cell
Volume: 9
Issue: 1
Start page: 47
End page: 62
Abstract: Glycosylation of the Fc region of IgG has a profound impact on the safety and clinical efficacy of therapeutic antibodies. While the biantennary complex-type oligosaccharide attached to Asn297 of the Fc is essential for antibody effector functions, fucose and outer-arm sugars attached to the core heptasaccharide that generate structural heterogeneity (glycoforms) exhibit unique biological activities. Hence, efficient and quantitative glycan analysis techniques have been increasingly important for the development and quality control of therapeutic antibodies, and glycan profiles of the Fc are recognized as critical quality attributes. In the past decade our understanding of the influence of glycosylation on the structure/function of IgG-Fc has grown rapidly through X-ray crystallographic and nuclear magnetic resonance studies, which provides possibilities for the design of novel antibody therapeutics. Furthermore, the chemoenzymatic glycoengineering approach using endoglycosidase-based glycosynthases may facilitate the development of homogeneous IgG glycoforms with desirable functionality as next-generation therapeutic antibodies. Thus, the Fc glycans are fertile ground for the improvement of the safety, functionality, and efficacy of therapeutic IgG antibodies in the era of precision medicine.
Rights: © The Author(s) 2017
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
DOI(Published Version): 10.1007/s13238-017-0433-3
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