BOC Sciences can synthesize site-specific antibody-drug conjugate (ADC) using unnatural amino acids (ncAA) that have orthogonal chemical reactivity with standard amino acids. We introduce unnatural amino acid residues in the antibody to upregulate drug conjugation specificity. With our extensive experience in antibody engineering and pharmaceuticals, BOC Sciences' professional research team is capable of providing customers with various personalized services.
Fig. 1. Unnatural amino acids conjugation strategies.
Unnatural amino acids can be used as a chemical treatment for biological conjugation due to their unique chemical properties compared with natural amino acids. These unnatural amino acids of unique chemical structures enable the introduction of linker-payload complexes chemoselectively. Moreover, this technology requires reorganizing antibody sequences and using tRNA and aminoacyl tRNA synthetase (aaRS) orthogonal to all endogenous tRNAs and synthetases in the host cell; thus, to bring unnatural amino acids into the protein in response to unassigned codons. Usually, the unnatural amino acid is added to the culture medium during the fermentation process. Therefore it is important to select the appropriate unnatural amino acids due to their related immunogenicity. Commonly used unnatural amino acids are analogs of natural amino acids that contain unique groups, such as ketones, azides, cyclopropenes, or dienes.
Studies have successfully integrated p-acetylphenylalanine (pAcF) as an unnatural amino acid residue in the antibody, and it contains a ketone functional group does not present in natural amino acids. An oxime bond can be formed between the ketone group and the alkoxyamine, which is highly stable under physiological conditions. Auristain glycoside payload is effectively coupled to the antibody through oxime linkage, generating a chemically uniform ADC. BOC Sciences' ADCs service platform can provide a variety of ketone-containing unnatural amino acids modification strategies for our customers to choose from.
Azides containing unnatural amino acids is another commonly used technique for research and development. Under physiological conditions, the widely used p-azidopiperidine (pAzF) can quickly perform CuAAC or SPAAC reactions, and this strategy can be used to successfully conjugate glucocorticoid payloads on anti-CD74 antibodies. In addition to pAcF technology, azide-containing lysine analogs were successfully introduced into the antibody to produce site-specific ADCs with Auristain glycoside payload, PBD dimer, or tubulin payloads. The ADCs service platform of BOC Sciences provides advanced and comprehensive azides unnatural amino acids modification services for your research projects.
Lysine cyclopropene derivatives and naturally occurring atypical amino acids such as selenocysteine (Sec) have been successfully integrated into the antibody. The resulting ADC showed good stability, selectivity, as well as in vitro and in vivo activities. As a leading service provider in the antibody-drug conjugate field, BOC Sciences has offered a full range of cyclopropenes unnatural amino acids modification services to our clients worldwide for years.