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Non-Genetic Generation of Antibody Conjugates Based on Chemoenzymatic Tyrosine Click Chemistry. 2021
Jorick J Bruins, and
Johannes A M Damen, and
Marloes A Wijdeven, and
Lianne P W M Lelieveldt, and
Floris L van Delft, and
Bauke Albada
Laboratory of Organic Chemistry, Wageningen University & Research, Stippeneng 4, 6708 WE, Wageningen, The Netherlands.
The availability of tools to generate homogeneous and stable antibody conjugates without recombinant DNA technology is a valuable asset in fields spanning from in vitro diagnostics to in vivo imaging and therapeutics. We present here a general approach for the conjugation to human IgG1 antibodies, by employing a straightforward two-stage protocol based on antibody deglycosylation followed by tyrosinase-mediated ortho-quinone strain-promoted click chemistry. The technology is validated by the efficient and clean generation of highly potent DAR2 and DAR4 antibody-drug conjugates (ADCs) with cytotoxic payloads MMAE or PBD dimer, and their in vitro evaluation.
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