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Oxidation in the complementarity-determining regions differentially influences the properties of therapeutic antibodies

Therapeutic antibodies can undergo a variety of chemical modification reactions in vitro. Depending on the site of modification, either antigen binding or Fc-mediated functions can be affected. Oxidation of tryptophan residues is one of the post-translational modifications leading to altered antibod...

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Autores principales: Dashivets, Tetyana, Stracke, Jan, Dengl, Stefan, Knaupp, Alexander, Pollmann, Jan, Buchner, Johannes, Schlothauer, Tilman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098445/
https://www.ncbi.nlm.nih.gov/pubmed/27612038
http://dx.doi.org/10.1080/19420862.2016.1231277
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author Dashivets, Tetyana
Stracke, Jan
Dengl, Stefan
Knaupp, Alexander
Pollmann, Jan
Buchner, Johannes
Schlothauer, Tilman
author_facet Dashivets, Tetyana
Stracke, Jan
Dengl, Stefan
Knaupp, Alexander
Pollmann, Jan
Buchner, Johannes
Schlothauer, Tilman
author_sort Dashivets, Tetyana
collection PubMed
description Therapeutic antibodies can undergo a variety of chemical modification reactions in vitro. Depending on the site of modification, either antigen binding or Fc-mediated functions can be affected. Oxidation of tryptophan residues is one of the post-translational modifications leading to altered antibody functionality. In this study, we examined the structural and functional properties of a therapeutic antibody construct and 2 affinity matured variants thereof. Two of the 3 antibodies carry an oxidation-prone tryptophan residue in the complementarity-determining region of the V(L) domain. We demonstrate the differences in the stability and bioactivity of the 3 antibodies, and reveal differential degradation pathways for the antibodies susceptible to oxidation.
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spelling pubmed-50984452016-11-23 Oxidation in the complementarity-determining regions differentially influences the properties of therapeutic antibodies Dashivets, Tetyana Stracke, Jan Dengl, Stefan Knaupp, Alexander Pollmann, Jan Buchner, Johannes Schlothauer, Tilman MAbs Report Therapeutic antibodies can undergo a variety of chemical modification reactions in vitro. Depending on the site of modification, either antigen binding or Fc-mediated functions can be affected. Oxidation of tryptophan residues is one of the post-translational modifications leading to altered antibody functionality. In this study, we examined the structural and functional properties of a therapeutic antibody construct and 2 affinity matured variants thereof. Two of the 3 antibodies carry an oxidation-prone tryptophan residue in the complementarity-determining region of the V(L) domain. We demonstrate the differences in the stability and bioactivity of the 3 antibodies, and reveal differential degradation pathways for the antibodies susceptible to oxidation. Taylor & Francis 2016-09-09 /pmc/articles/PMC5098445/ /pubmed/27612038 http://dx.doi.org/10.1080/19420862.2016.1231277 Text en © 2016 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Report
Dashivets, Tetyana
Stracke, Jan
Dengl, Stefan
Knaupp, Alexander
Pollmann, Jan
Buchner, Johannes
Schlothauer, Tilman
Oxidation in the complementarity-determining regions differentially influences the properties of therapeutic antibodies
title Oxidation in the complementarity-determining regions differentially influences the properties of therapeutic antibodies
title_full Oxidation in the complementarity-determining regions differentially influences the properties of therapeutic antibodies
title_fullStr Oxidation in the complementarity-determining regions differentially influences the properties of therapeutic antibodies
title_full_unstemmed Oxidation in the complementarity-determining regions differentially influences the properties of therapeutic antibodies
title_short Oxidation in the complementarity-determining regions differentially influences the properties of therapeutic antibodies
title_sort oxidation in the complementarity-determining regions differentially influences the properties of therapeutic antibodies
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098445/
https://www.ncbi.nlm.nih.gov/pubmed/27612038
http://dx.doi.org/10.1080/19420862.2016.1231277
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