The glycosylation modifications to the constant domain are crucial to antibody activities and their effector functions since that glycosylation alters the affinity of antibodies to Fc receptors. With integrated antibody development and engineering techniques, Creative Biolabs offers comprehensive glycosylation services for non-IgG antibodies (IgA, IgM, and IgE). We tailor our services to develop high-quality glycosylated antibodies applied for multiple hot diagnostics. They direct against a variety of disease targets with low cross-reactivity, promoting the development of immunology methods to meet the needs of our valued clients.
Glycosylation, a type of post-translational modification, is an enzymatic process that glycan sugars are attached to a functional group of other glycans, lipids, proteins or other organic molecules. In the body, glycosylation mainly takes place in the Golgi apparatus and endoplasmic reticulum, which occurs as the result of the synchronized action of glycosylation enzymes. O‑linked and N‑linked glycosylation are the two most common mechanisms through which glycans can be linked to lipids and proteins. Due to the difference in structure, length, composition, and glycosidic bond of the glycans, glycosylation engineering greatly increases diversity in the proteins and finely affects the activity of the modified molecules.
Therapeutic antibody is a class of monoclonal antibodies (mAbs) that bind to cells or proteins mono-specifically, which has achieved great success through technological breakthroughs. Glycosylation modifications of the Fc region, or the Fab region in some cases, can further enhance the effector functions and have a profound impact on the diversity, safety, immunogenicity, stability, and clinical efficacy of these therapeutic antibodies. Antibody glycoengineering is an important method to improve the pharmacological properties of therapeutic mAbs. However, the majority of approved or under-researched therapeutic antibodies are IgG isotypes, and engineering techniques focus on IgG mAb glycol-modification over the past decades. Actually, the glycosylation sites and glycoengineering of five antibody isotypes are quite different. The most obvious difference is that glycosylation sites of these non-IgG antibodies are more than IgG isotype. Development of glycosylated non-IgG antibodies (mainly IgA, IgM, and IgE) to improve their performance and therapeutic effects is necessary and imperative.
Fig.1 Diagrammatic glycosylation sites representations of IgM, IgA1, IgA2m(2), IgG1, IgD, and IgE. (Arnold, 2007)
Our Glycosylated Non-IgG Antibody Services
Alteration of glycan compositions and structures of the antibody Fc domain can lead to conformational changes, which could change binding affinity to Fc receptors, resulting in changes of effector functions, such as complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and antibody-dependent cell-mediated phagocytosis (ADCP). In order to optimize bioactivities and effector functions of these non-IgG therapeutic antibodies, Creative Biolabs has successfully constructed an antibody glycoengineering platform to provide high-quality non-IgG (mainly IgA, IgM, and IgE) antibody glycosylation characterization and glycan profiling services.
There are two subclasses of IgA antibody, IgA1 and IgA2, both of which are more heavily glycosylated than IgG. Not only the number of IgA glycosylation sites is higher than IgG isotype, but the formation is also more complex (consisting of both N-glycosylation and O-glycosylation, and all of these are also orientated towards the outside of the molecule).
Polymeric IgM is a heavily glycosylated antibody with five N-linked glycosylation sites in each heavy chain. The J chain of pentameric IgM contains an additional single N-linked glycosylation site. These glycosylations are pivotal to IgM secretion, complement activation, and B cell surface presentation.
In human IgE monomeric antibody, there are seven glycosylation sites in each heavy chain, of which carbohydrates account for approximately 12% of their molecular weight, making IgE the most heavily glycosylated antibody in all isotypes. Notably, glycosylation sites in human IgE are different from that in murine, which possess nine N-linked glycosylation sites.
Fig.2 An example of sequential processing of the antibody glycan. (Jennewein, 2017)
Creative Biolabs is specialized in the development of antibodies that are suitable for a number of diseases detection and analysis. Given the potential for glycosylation to benefit therapeutics, now we provide a full range of non-IgG glycosylated antibodies (IgA, IgM, and IgE) that produced by specific expression systems. Moreover, we offer related non-IgG antibody products and customized application services for our clients to meet every specific research requirement. Please contact us to experience our first-class expert services.
- Arnold, J.N.; et al. The Impact of Glycosylation on the Biological Function and Structure of Human Immunoglobulins. Annual Review of Immunology. 2007, 25(1): 21-50.
- Jennewein, M.F.; Alter, G. The immunoregulatory roles of antibody glycosylation. Trends in immunology. 2017, 38(5): 358-372.
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