Covalent and noncovalent bioconjugation chemistries are the main strategies for the preparation of antibody bioconjugates for various applications. With years of experience in antibody modification and bioconjugation, Creative Biolabs now provides a full range of conjugation strategies to help clients develop customized antibody-oligonucleotide conjugates (AOCs) in a time- and cost-efficient way.
A non-covalent bond is a special type of chemical bond which does not involve the sharing of a pair of electrons. Noncovalent interactions include affinity interactions, electrostatic, metal-mediated coordination, hydrophobic, and hydrogen bonding. Noncovalent approaches rely heavily on physical interactions via intermolecular noncovalent forces. The forces are weak by nature and they must work together to have a significant effect, namely cooperative effect. In recent years, advances in exploiting noncovalent interactions have led to the design of sophisticated biomolecules with complex architectures. Covalent-based synthetic methods become increasingly tedious as macromolecular structures and functional materials continue to evolve with a higher level of complexity and function. Noncovalent chemistries can overcome some of the drawbacks of covalent strategies such as lengthy synthesis and reagents’ incompatibility. Currently, there are some widely-used methods include streptavidin-biotin and protein A/G-Fc mAb universal adapters.
Many supramolecular bioconjugation strategies employ biological recognition motifs, which are almost perfect guest-host systems. A classic example of such a system is the biotin-(strept) avidin interaction. Due to its small size (244.3 Da) and good stability, biotin can be easily noncovalently conjugated with many proteins, antibodies, polymers without any significant change in their biological activities.
Antibody binding proteins such as protein A and protein G could also be used for antibody conjugation. For instance, the incorporation of additional unpaired cysteine residues into the backbone of protein A/G is a valuable strategy for maleimide-tagged ON conjugation.
The covalent bond is the most common form of linkage between atoms in organic chemistry and biochemistry. The reaction of one functional group with another leads to the formation of a covalent bond via the sharing of electrons between atoms. Classical covalent bioconjugation approaches for the preparation of antibody conjugates are based on conjugation to either lysine residues, naturally present in native antibodies, or cysteine residues, which can, for example, be generated through reduction of interchain disulfide bonds. Nevertheless, these techniques afford heterogeneous mixtures comprising conjugate species with varying ON-to-antibody ratios. To generate more homogeneous AOCs, novel protein engineering and enzymatic approaches for conjugation have been actively developed and these techniques have been successfully applied for the preparation of site-specific AOCs. The following conjugation methods are the most commonly used to prepare AOCs.
Fig.1 Streptavidin-based strategies for targeted drug delivery. (Dundas, 2013)
Noncovalent Conjugation | Covalent Conjugation | |
Advantages |
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Disadvantages |
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Relatively complex processes and procedures |
While a number of both covalent and noncovalent approaches exist to prepare AOCs, the choice of the appropriate conjugation method in each case usually depends on the specific purpose. If you are interested in our conjugation strategies for AOC development, please feel free to contact us for more information.
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