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 |
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container_title | Bioconjugate chemistry |
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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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Published by American Chemical Society</rights><rights>Copyright American Chemical Society Oct 20, 2021</rights><rights>2021 The Authors. 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M</creatorcontrib><creatorcontrib>Wijdeven, Marloes A</creatorcontrib><creatorcontrib>Lelieveldt, Lianne P. W. M</creatorcontrib><creatorcontrib>van Delft, Floris L</creatorcontrib><creatorcontrib>Albada, Bauke</creatorcontrib><title>Non-Genetic Generation of Antibody Conjugates Based on Chemoenzymatic Tyrosine Click Chemistry</title><title>Bioconjugate chemistry</title><addtitle>Bioconjugate Chem</addtitle><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.</description><subject>Antibodies</subject><subject>Cell Line, Tumor</subject><subject>Chemical synthesis</subject><subject>Click Chemistry</subject><subject>Conjugates</subject><subject>Conjugation</subject><subject>Cytotoxicity</subject><subject>Deglycosylation</subject><subject>Dimers</subject><subject>Glycosylation</subject><subject>Humans</subject><subject>Immunoconjugates - chemistry</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - chemistry</subject><subject>Monophenol Monooxygenase - chemistry</subject><subject>Monophenol Monooxygenase - metabolism</subject><subject>Oligopeptides</subject><subject>Payloads</subject><subject>Quinones</subject><subject>Recombinant DNA</subject><subject>Tyrosinase</subject><subject>Tyrosine</subject><subject>Tyrosine - chemistry</subject><issn>1043-1802</issn><issn>1520-4812</issn><issn>1520-4812</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhq0KRL_4CyUSFy5ZPHacOBekEvUDqYJLe8VynEnrJWsXO0EKv75Od1kVLpzG0jzzzrx-CXkHdAWUwUdt4qq13ni3Ng-4WYGhlAs4IEcgGM0LCexVetOC5yApOyTHMa4ppTVI9oYc8kJAXVTVEfn-1bv8Ch2O1mRLDXq03mW-z87daFvfzVmTtkz3esSYfdYRuyz1m7TVo_s9b_QyeTsHH63DrBms-fHctXEM8yl53esh4ttdPSF3lxe3zXV-8-3qS3N-k-tC1mMuade1mqZTu1pAaaSoORRY0rKrqr5nNdeyRY6s1rIEUWAy0ve0x44nshD8hHza6j5O7QY7g24MelCPwW50mJXXVv3dcfZB3ftfSgrOACAJfNgJBP9zwjiqZMDgMGiHfoqKiYoJJkqoEvr-H3Ttp-CSvUTJUpRUVAtVbSmTfiYG7PfHAFVLhiplqF5kqHYZpsmzl172c39CSwDfAovCfvf_ZJ8AXlau-Q</recordid><startdate>20211020</startdate><enddate>20211020</enddate><creator>Bruins, Jorick J</creator><creator>Damen, Johannes A. 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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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