Toshihiko Katoh
Radka Saldova
Roisin O'Flaherty
Tomonori Izumi
Yuka Mimura-Kimura
Toshiaki Utsunomiya
Yoichi Mizukami
Kenji Yamamoto
Tsuneo Matsumoto
Pauline M. Rudd
1 Department of Clinical Research, NHO Yamaguchi-Ube Medical Center, 685 Higashi-Kiwa, Ube 755-0241, Japan;
2 Laboratory of Molecular Biology and Bioresponse, Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kitashirakawa, Oiwake-Cho, Sakyo-Ku, Kyoto 606-8502, Japan;
3 NIBRT GlycoScience Group, National Institute for Bioprocessing Research and Training, Mount Merrion, Blackrock, Dublin 4, Ireland;
4 Center for Regenerative Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube 755-8505, Japan;
5 Center for Gene Research, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan;
6 Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, 1-308 Suematsu, Nonoichi, Ishikawa 921-8836, Japan
Funds: This study was supported by JSPS KAKENHI grant No. 23590578 (Y. M.), the Science Foundation Ireland Starting Investigator Research grant (SFI SIRG) under grant No. 13/SIRG/2164 (R. S.), and EU FP7 program HighGlycan grant No. 278535 (R. O.).
Received Date: 2017-04-04
Rev Recd Date:2017-05-22
Abstract
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 nextgeneration 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.Keywords: chemoenzymatic glycoengineering,
crystal structure,
endoglycosidase,
fucose,
glycosylation,
intravenous immunoglobulin,
sialic acid,
transglycosylation,
ultra performance liquid chromatography
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