BOC Sciences can synthesize site-specific antibody-drug conjugate (ADC) using unnatural amino acids that have orthogonal chemical reactivity with standard amino acids. We introduce unnatural amino acid residues in the antibody by biological means in order to increase the specificity of drug coupling. With a rich background in antibody engineering and pharmaceuticals, as well as a professional team, BOC Sciences can provide customers with a variety of personalized services.
Biological orthogonal reactions are those chemical reactions that can be carried out in living cells or tissues without interfering with the biological biochemical reactions. The introduction of unnatural amino acid - p-acetylphenylalanine (pAcPhe) through biological orthogonal reaction is another commonly used point coupling method. The method uses an evolved tyrosyl-tRNA/aminoacyl-tRNA synthetase that specifically recognizes unnatural amino acids and transfects Chinese hamster ovary cells (CHO) to replace the 21st amino acid of the amber codon. The resulting cells can be used to synthesize various antibodies with gene-coding-p-acetylphenylalanine residues.
A site-specific antibody-drug conjugate was prepared by site-directed coupling of p-acetophenine to a Fab fragment of an anti-Her2 antibody or full-length IgG1 followed by a hydrazone bond to auristatin. The resulting conjugates have excellent pharmacokinetic properties, potential in vitro anti-Her2+ cell activity, and can reduce tumor volume in transplanted mice. By site-directed coupling to auristatin by introducing pAcPhe into anti-CXCR4 IgG, the half-effect concentration (EC50) of the site-specific CXCR4-auristatin ADCs is approximately (80-100) ×10−12 mol·L−1. It can be used in the treatment of various metastatic cancers.