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Synthesis of Bispecific Antibodies using Genetically Encoded Unnatural Amino Acids

Author:
Kim, Chan Hyuk, Axup, Jun Y., Dubrovska, Anna, Kazane, Stephanie A., Hutchins, Benjamin A., Wold, Erik D., Smider, Vaughn V., Schultz, Peter G.
Source:
Journal of the American Chemical Society 2012 v.134 no.24 pp. 9918-9921
ISSN:
1520-5126
Subject:
amino acids, antibodies, crosslinking, cytotoxicity
Abstract:
Bispecific antibodies were constructed using genetically encoded unnatural amino acids with orthogonal chemical reactivity. A two-step process afforded homogeneous products in excellent yield. Using this approach, we synthesized an anti-HER2/anti-CD3 bispecific antibody, which efficiently cross-linked HER2+ cells and CD3+ cells. In vitro effector-cell mediated cytotoxicity was observed at picomolar concentrations.
Agid:
5385754