Terminal sialic acid residues affect antibody efficacy. CD BioGlyco has developed effective Antibody Remodeling strategies. We provide our clients with remodeling antibody services with homogeneous G2S2 glycoform.
Antibodies are an important part of the human immune system and are involved in defending against foreign substances and pathogens. All human antibodies are glycoproteins with varying degrees of glycosylation, carrying at least one or more conserved N-glycans in the crystallizable fragment (Fc) domain. These glycans are often present as mixtures of heterogeneous glycoforms and have profound effects on the biological function and therapeutic efficacy of antibodies. The N-glycans of immunoglobulin G (IgG) contain a complex biantennary heptasaccharide core structure consisting of four N-acetylglucosamine (GlcNAc) and three mannoses, as well as other possible monosaccharides such as galactose, bisecting GlcNAc, fucose, and sialic acid.
Fig.1 Structure of IgG. (Boune, et al., 2020)
Sialic acid is linked to the terminal galactose of human serum IgG via α-2,3 or α-2,6 bonds, accounting for about 11%-15% of IgG-Fc glycans. It is found that the sialic acid residues at the Fc terminus are highly dynamic and do not strongly interact with the protein. However, the anti-inflammatory properties of Fc-sialylated glycans have attracted more and more researchers' attention. Fc sialylated intravenous Ig (IVIG) is used not only to treat immunodeficiency diseases but also to treat autoimmune diseases such as idiopathic thrombocytopenic purpura. In addition, Fc sialylation affects the effector function of antibodies. Sialylated IgG has a reduced affinity for Fcγ receptor III (FcγRIII), resulting in reduced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
Sialylated Fc not only contributes to the anti-inflammatory properties of the antibody but affects the effector function of the antibody. To better study sialylated IgG, it is necessary to modify the heteroglycan of a given glycoprotein by chemoenzymatic glycoengineering strategies. CD BioGlyco integrates multiple advanced technologies to develop efficient Antibody Glycoengineering strategies. We provide our clients with human IgG (including human IgG1, IgG2, and IgG4) of the homogeneous Fc G2S2 glycoform. Our workflow is as follows:
1) Trim Fc glycans to the innermost GlcNAc by IgG-specific endoglycosidases.
2) Glycosynthase catalyzes the reaction of pre-assembled G2S2 glycan oxazoline with core GlcNAc to generate human IgG with homologous G2S2 glycoforms.
Fig.2 Process of remodeling an antibody with G2S2 Glycoform. (CD BioGlyco)
CD BioGlyco has been committed to glycoengineering research for many years and has developed a first-class Glycoengineering platform. If you are interested in remodeling antibody services with G2S2 glycoforms, please feel free to contact us.
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