Non-Genetic Generation of Antibody Conjugates Based on Chemoenzymatic Tyrosine Click Chemistry

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, b...

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Veröffentlicht in:Bioconjugate chemistry 2021-10, Vol.32 (10), p.2167-2172
Hauptverfasser: Bruins, Jorick J, Damen, Johannes A. M, Wijdeven, Marloes A, Lelieveldt, Lianne P. W. M, van Delft, Floris L, Albada, Bauke
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container_end_page 2172
container_issue 10
container_start_page 2167
container_title Bioconjugate chemistry
container_volume 32
creator Bruins, Jorick J
Damen, Johannes A. M
Wijdeven, Marloes A
Lelieveldt, Lianne P. W. M
van Delft, Floris L
Albada, Bauke
description 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.
doi_str_mv 10.1021/acs.bioconjchem.1c00351
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source MEDLINE; ACS Publications
subjects Antibodies
Cell Line, Tumor
Chemical synthesis
Click Chemistry
Conjugates
Conjugation
Cytotoxicity
Deglycosylation
Dimers
Glycosylation
Humans
Immunoconjugates - chemistry
Immunoglobulin G
Immunoglobulin G - chemistry
Monophenol Monooxygenase - chemistry
Monophenol Monooxygenase - metabolism
Oligopeptides
Payloads
Quinones
Recombinant DNA
Tyrosinase
Tyrosine
Tyrosine - chemistry
title Non-Genetic Generation of Antibody Conjugates Based on Chemoenzymatic Tyrosine Click Chemistry
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