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BOC Sciences possesses unparalleled expertise in Antibody-Drug Conjugates (ADCs) production. Besides cysteine conjugation, lysine conjugation, carbohydrate conjugation, and non-natural amino acids conjugation, we also offer other coupling techniques, including enzymatic modified antibodies and others. BOC Sciences has established a one-stop integrated antibody and drug platform to provide optimum antibody engineering and conjugation services.
Enzymatic modified antibodies can be used for site-specific conjugation. In this approach, enzymes that recognize specific amino acid markers are developed for site-specific antibody conjugation. Moreover, the payload attachment can be achieved selectively by inserting specific amino acid tags in the antibody sequence. These tags are recognized by specific enzymes, such as a formylglycine-generating enzyme (FGE), microbial transglutaminase (MTG), transpeptidase or tyrosinase, to enable site-specific conjugation. As a global biotechnology company, BOC Sciences is capable of designing and implementing the most appropriate conjugation strategy for your ADC development. Our team of professionals has years of experience in manufacturing therapeutic agents and has enabled us to support your scientific and clinical uses of ADCs.
Fig. 1. Enzyme-modified antibody conjugation strategies.
Glycosyltransferase is a large family of proteins involved in oligosaccharides synthesis that are responsible for the transfer of glycosyl residues from activated sugar nucleotides to glycoconjugates, glycoproteins, or liposomes. BOC Sciences can synthesize site-specific antibody-drug conjugates via glycosyltransferase. This technique utilizes mutated glycosyl groups and attaches to chemically active glycosyl groups at a position where the antibodies can undergo glycosylation reaction, subsequently site-coupled with drug molecules to generate ADCs.
The microbial transglutaminase strategy is also often used in developing site-specific conjugation. Microbial transglutaminase catalyzes a peptide bond formation between the glutamine side chain of desugared antibody position 295 and the primary amine of the substrate. Compared with other enzymatic strategies, microbial transglutaminase is a flexible technique that does not require peptide donors to achieve conjugation, and there is no structural limitation as long as the acyl acceptor contains a primary amine. As an expert in ADCs conjugation services, BOC Sciences can provide comprehensive assistance for your transglutaminase conjugation developments.
BOC Sciences has established an advanced one-stop ADC service platform to provide technical services related to conjugation technologies, including formylglycine mediated conjugation service. Formylglycine mediated conjugation technology utilizes a gene-encoded pentapeptide sequence (Cys-X-Pro-X-Arg), in which cysteine residues are recognized by FGE and are co-translated and oxidized to formylglycine during protein expression. Thus, the engineered antibody is selectively conjugated to the aldehyde-specific linker through the Hydrazino-Pictet-Spengler Ligation method.
As a leading service provider in drug discovery and development, BOC Sciences can provide sortase-mediated conjugation services to companies and research organizations specializing in ADC novel drug research and development. This strategy adapts sortase A from S Staphylococcus aureus to cleave the amide bond between threonine and glycine residues on the C-terminal pentapeptide sequence (LPXTG). Subsequently, it catalyzes the conjugation of glycine-related payload to the newly generated C-terminus and forms peptide bonds at physiological temperature and pH. This method can be applied to different antibodies.
Another emerging new method is site-specific antibody labeling through tyrosine tags, in which the tyrosine tag is fused to the C-terminus of the monoclonal antibody's light chain. In consideration of site accessibility, engineered tetra-glycyltyrosine residue was used as a label that provides an accessible conjugation site. Moreover, tyrosinase oxidizes tyrosine to 1,2-quinone and allows cycloaddition reactions with various bicyclo-[6.1.0]-nonyne (BCN) derivatives. This method can be effectively conjugated with MMAE containing a BCN linker. BOC Sciences provides customized and reliable solutions that efficiently couple tyrosine and payload to meet your specifications.
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