The traditional antibody modifications may affect the structure of the antibody-specific recognition region, resulting in reduced antibodies' ability to recognize the antigen. CD BioGlyco provides a service that conjugates azide to site-specific antibodies especially Human IgG1-4, IgG from animals (mouse, rat, rabbit, monkey, sheep, goat, cow, and horse), and Fc-fusion proteins. This conjugation occurs in the Fc region and does not affect the recognition of the antigen by the antibody, while the conjugated azide can undergo a subsequent click reaction for binding to the drug of interest. We have the confidence to become your best scenic research assistant in the field of site-specific ADC (antibody-drug conjugate) study.
The concept of click chemistry, first articulated by Sharpless and his colleagues in 2001, is essentially the use of uncomplicated chemical reactions to assemble small molecular units. It harnesses the power of molecular assembly to make molecular connections easier. "Click" conveys a sense of convenience and satisfaction provided by attaching the item to the luggage strap connector. It doesn't matter what the units are, if the two ends of the units can "click" on each other, they are linked. The foundational reactions of click chemistry are including conjugate addition, strained ring opening, acylation/sulfonylation, aldehyde capture by α-effect nucleophiles, cycloaddition, and azide-alkyne cycloaddition.
Fig.1 Click Chemistry. (Devaraj & Finn, 2021)
Azides are molecules that are energy-rich and have many applications. Organic azides are able to perform a wide variety of organic reactions and are an important part of the azide-alkyne "click" reaction. Currently, azide click chemistry is a very popular chemical method. The 2nd generation of azide click chemistry removes the need to use copper by reacting azide molecules with structurally restricted alkynes such as DBCO (Dibenzocyclooctyne) or BCN (Bicyclo[6.1.0]nonene) molecules. Now azide click chemistry is widely used in pharmaceuticals and biotechnology due to its mild conditions, rapidity, and biocompatibility.
Fig.2 Chemical structure of azide. (Wikimedia Commons)
Antibody-drug conjugate (ADC) is a novel targeted drug research direction. Its basic components are site-specific monoclonal antibodies and potent cytotoxic drugs interconnected by chemical junctions, which provide an accurate way to release cytotoxic drugs to kill cells effectively. Using azide click chemistry, site-specific antibodies and cytotoxic drugs can be conjugated to produce ADCs. Monoclonal antibodies are the main components of the ADC structure and should target specific unique antigens with minimal cross-reactivity and immunogenicity with other cells. Cytotoxic drugs are often referred to as payload, cytotoxic drugs are mainly microtubule disrupting agents (Monomethyl auristatin E, MMAE) or DNA damaging agents (PNU Anthracycline). They should have high stability in systemic circulation and lysosomes, low immunogenicity, small molecular weight and long half-life. The function of linker is to link monoclonal antibodies to cytotoxic drugs. The linker must be stable in the systemic circulation and able to cleave efficiently within the target cell to release the cytotoxic drug. Normally, linker can be divided into two main subtypes: non-cutable joints and cutable joints.
Fig.3 The three components of ADCs: the monoclonal antibody, cytotoxic drug (payload), and the linker. (Abuhelwa et al., 2022)
CD BioGlyco's Site-Specific Antibody Conjugation is a technology based on Fc glycan remodeling and click chemistry. This azide conjugation occurs on the N-linked glycosylation site of the Fc region, it is a sort of Glycan Oxidation-based ADC Development. Before conjugating azide activation to site-specific antibodies, all the Fc N-glycans must be removed until the innermost GalNAz, followed by azide activation conjugated at the GalNAz site. Glycan Enzymatic Modification-based ADC Development and Glycoengineering-based ADC Development are also suitable for you to optimize your ADCs, they can be used in combination with this service to help your research.
We produce site-specific antibody conjugation with azide activation, to provide sites for subsequent azide click chemistry reactions. Based on this service, we also provide site-specific antibody conjugation with MMAE and site-specific antibody conjugation with PNU Anthracycline. These two classical and typical cytotoxic drugs conjugated to antibodies to produce ADCs will help your research in the field of ADCs.
Services we provide include but are not limited to:
Our azide conjugation technology does not introduce copper and can be highly efficient and specific at the Fc N-linked glycosylation site of the antibody. And each antibody has four degrees of labeling (DOL). Moreover, CD BioGlyco's site-specific antibody conjugation service has a cleavable glycopeptide linker, which is activated by lysosomes in a two-step reaction to control drug release in target cells, it can reduce drug instability and off-target effects. We have outstanding scientists specializing in this service.
CD BioGlyco has advanced site-specific ADC production technology, and we have the confidence to meet customers' requirements about conjugating different antibodies to azide. If you are interested in our services, please contact us for more detailed information.
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