| RRC ID |
66073
|
| Author |
Takashima S, Kurogochi M, Tsukimura W, Mori M, Osumi K, Sugawara SI, Amano J, Mizuno M, Takada Y, Matsuda A.
|
| Title |
Preparation and biological activities of anti-HER2 monoclonal antibodies with multibranched complex-type N-glycans.
|
| Journal |
Glycobiology
|
| Abstract |
Immunoglobulin G (IgG) has a conserved N-glycosylation site at Asn297 in the fragment crystallizable (Fc) region. Previous studies have shown that N-glycosylation of this site is a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity. While the N-glycan structures attached to the IgG-Fc region are generally heterogenous, IgGs engineered to be homogenously glycosylated with functional N-glycans may improve the efficacy of antibodies. The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multi-branched complex-type N-glycans are not typically found. However, IgGs with tri-antennary complex-type N-glycans have been generated using the N-glycan remodeling technique, suggesting that more branched N-glycans might be artificially attached. At present, little is known about the properties of these IgGs. In this study, IgGs with multi-branched N-glycans on the Fc region were prepared by using a combination of the glycosynthase/oxazoline substrate-based N-glycan remodeling technique and successive reactions with glycosyltransferases. Among the IgGs produced by these methods, the largest N-glycan attached was a bisecting N-acetylglucosamine (GlcNAc) containing a sialylated penta-antennary structure. Concerning the Fc-mediated effector functions, the majority of IgGs with tri- and tetra-antennary N-glycans on their Fc region showed properties similar to IgGs with ordinary bi-antennary N-glycans.
|
| Volume |
31(10)
|
| Pages |
1401-1414
|
| Published |
2021-11-18
|
| DOI |
10.1093/glycob/cwab064
|
| PII |
6311236
|
| PMID |
34192331
|
| MeSH |
Acetylglucosamine / immunology
Humans
Immunoglobulin Fc Fragments / immunology*
Immunoglobulin G / immunology*
Polysaccharides / immunology*
Receptor, ErbB-2 / immunology*
|
| IF |
4.06
|
| Resource |
| Human and Animal Cells |
293(RCB1637) |
