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

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_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.

SUBMITTER: Dashivets T

PROVIDER: S-EPMC5098445 | biostudies-literature | 2016 Nov/Dec

REPOSITORIES: biostudies-literature

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

Dashivets Tetyana T Stracke Jan J Dengl Stefan S Knaupp Alexander A Pollmann Jan J Buchner Johannes J Schlothauer Tilman T

mAbs 20160909 8

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 oxida ...[more]

PMID: 27612038

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