Oxidation in the Complementarity-determining Regions Differentially Influences the Properties of Therapeutic Antibodies

Overview

Journal MAbs

Specialty Allergy & Immunology

Date 2016 Sep 10

PMID 27612038

Citations 22

Authors

Tetyana Dashivets

Jan Stracke

Stefan Dengl

Alexander Knaupp

Jan Pollmann

Johannes Buchner

Tilman Schlothauer

Affiliations

Soon will be listed here.

Abstract

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 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.

Citing Articles

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In-Depth Characterization for Methionine Oxidization in Complementary Domain Region by Hydrophobic Interaction Chromatography.

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