N6-[(2-Azidoethoxy)carbonyl]-L-lysine

N⁶-[(2 - azidoethoxy) carbonyl]-L - lysine（CAS No.：1167421-25-1） is an unnatural amino acid carrying an azide group，which can be site-specifically incorporated into antibody proteins through a cell-based mammalian expression system to serve as a bioorthogonal reactive group for site-specific antibody conjugation；the terminal azide group on its side chain can undergo a click cycloaddition reaction to form a stable heterocyclic triazole linkage，enabling site-specific conjugation of toxins to antibodies，and addressing the high product heterogeneity and insufficient stability that limit dosing when antibody-drug conjugates（ADCs）are prepared by conventional random conjugation to antibody cysteine and lysine residues。In the preparation of anti-Her2/neu antibodies，this unnatural amino acid can be introduced at 4 different sites on the antibody，with conjugation efficiencies exceeding 95% at each site for toxins such as auristatin F and pyrrolobenzodiazepine（PBD）dimers，yielding homogeneous ADCs with a drug-to-antibody ratio ＞1.9；the resulting ADCs show potent，target-specific activity in in vitro cytotoxicity assays，the anti-Her2/neu conjugates exhibit good in vivo stability，and ADCs containing PBD toxins demonstrate potent antitumor activity in mouse tumor xenograft models；this technology can also be extended to produce fully functional ADCs carrying 4 toxin molecules per antibody，and the high stability of the azide - alkyne linkage combined with the site specificity of the expression system enables the production of ADCs with optimized pharmacokinetic、biological and biophysical properties。