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Antibody conjugation via one and two C-terminal selenocysteines.
|Title||Antibody conjugation via one and two C-terminal selenocysteines.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Li X, Yang J, Rader C|
|Journal||Methods (San Diego, Calif.)|
|Date Published||2013 Jun 10|
Conventional antibody conjugation methods generate antibody-drug conjugates that are heterogeneous mixtures with undefined stoichiometry and variable pharmacokinetic and pharmacodynamic properties. We have previously described a strategy to generate site-specific antibody conjugates by genetic engineering of an antibody with a single C-terminal selenocysteine, the 21st natural amino acid, which displays unique chemical reactivity allowing selective conjugation in the presence of all other natural amino acids. In the present work, we describe a method for expanding this technology to higher drug-to-antibody ratios by genetically engineering an antibody with two C-terminal selenocysteines. Both selenocysteines effectively conjugate to a fluorescent iodoacetamide derivative and the resulting conjugate fully retains its antigen binding capability. Our method provides a platform for creating stoichiometrically defined antibody-drug conjugates for therapeutic intervention.