In addition to thiomonoclonal antibody technology, the addition of non-standard amino acids (NCAA) provides another possibility for site-specific coupling. The technology uses amino acids with unique chemical structure, which can introduce linker payload complexes in a chemically selective manner. This technique requires the recombination of antibody sequences, using tRNA and aminoacyl tRNA synthetase (AARS) orthogonal […]
Site specific biological coupling of engineered antibodies Advances in bioorthogonal chemistry and protein engineering contribute to the generation of more uniform ADCs. Although there are many attachment methods available on natural monoclonal antibodies, site-specific biological coupling on engineered antibodies can more effectively control Dar and avoid changing the affinity for antigen binding. In this […]
Glycan coupling Because IgG is a glycoprotein, it contains an N-glycan at n297 of CH2 domain of each heavy chain of Fc fragment. This glycosylation can be used as the attachment point of connecting payload. The long-distance localization between polysaccharide and Fab region reduces the risk of damaging the antigen binding ability of antibody after […]
Endogenous coupling of amino acids One of the most common coupling methods is to use the lysine residue of the antibody, the amino acid nucleophilic NH2 group, to react with the electrophilic N-hydroxysuccinimide (NHS) Group on the lik payload. Although the reaction is simple, the high abundance of available lysine residues leads to the formation […]
The natural structure of monoclonal antibodies provides a variety of possibilities for biological coupling. Chemical and specific natural (non engineering) antibody coupling has some advantages. It can avoid the complexity of antibody specific site mutation and the possible challenges in the amplification and optimization of cell culture. Coupling sites according to the antibody sequence, the […]
Apoptosis inducer (BCL XL inhibitor) Overexpression of anti apoptotic Bcl-2 family members (including BCL XL) is one of the mechanisms for cancer cells to obtain apoptosis resistance. Drugs that block the BH3 binding domain on BCL XL can trigger cancer cell apoptosis. Telanstadine and its analogues Targeted spliceosome is a large ribonucleoprotein complex involved in […]
There are so many payloads, like MMAE, Calicheamicin, MMAF, DM1, SN-38 and Dxd. Pyrrole benzodiazepines and indole chlorobenzodiazepines Pyrrolo [2,1-c] [1,4] benzodiazepine (PBD) is a natural product with antitumor activity. Their mode of action is selective alkylation in small grooves of DNA, in which the N2 of guanine forms a covalent bond with the electrophilic […]
There are so many payloads, like MMAE, Calicheamicin, MMAF, DM1, SN-38 and Dxd. Calendula Auristatins is an important payload used in ADC. The most famous family member MMAE exists in two listed drugs, adcetris and Polivy. At present, more than 10 kinds of ADCs with calendula (such as MMAE) or methylcalendula f (MMAF) […]
There are so many payloads, like MMAE, Calicheamicin, MMAF, DM1, SN-38 and Dxd. Microtubule destroying drug 1. Calendula Auristatins is an important payload used in ADC. The most famous family member MMAE exists in two listed drugs, adcetris and Polivy. At present, more than 10 kinds of ADCs with calendula (such as MMAE) or methylcalendula […]
Table2. Chemical triggers Conjugate linker is not only the molecular part forming covalent connection between antibody and small molecule payload, but also the key element with design properties in targeted drug therapy. The addition of linkers should not induce aggregation, and it is necessary to ensure acceptable PK characteristics, limit the premature release (stability) of […]
