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Synthesis of bispecific antibodies using genetically encoded unnatural amino acids

Kim, C.H.; Axup, J.Y.; Dubrovska, A.; Kazane, S.A.; Hutchins, B.A.; Wold, E.D.; Smider, V.V.; Schultz, P.G.

Journal of the American Chemical Society 134(24): 9918-9921

2012

ISSN/ISBN: 1520-5126
PMID: 22642368
DOI: 10.1021/ja303904e
Accession: 056077258
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.

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