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Oxidation of therapeutic proteins and peptides: structural and biological consequences

Riccardo Torosantucci1, Christian Schöneich, Wim Jiskoot

  • 1Division of Drug Delivery Technology Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.

Pharmaceutical Research
|September 26, 2013
PubMed

Insights

Protein and peptide oxidation impacts drug development. Understanding oxidation

Area of Science:

  • Biopharmaceutical Development
  • Protein Chemistry
  • Drug Stability

Background:

  • Oxidation is a primary degradation route for therapeutic proteins and peptides.
  • This degradation occurs throughout the drug lifecycle, from production to patient administration.
  • Oxidative modifications can alter protein structure, function, and safety profiles.

Purpose of the Study:

  • To review the scientific literature on the structural and biological impacts of protein and peptide oxidation.
  • To highlight key examples of oxidized therapeutic products and their consequences.
  • To emphasize the importance of characterizing oxidation products in pharmaceutical development.

Main Methods:

  • Comprehensive literature review of scientific publications.
  • Analysis of structural and biological consequences of oxidation.
  • Discussion of specific therapeutic protein and peptide examples.

Main Results:

  • Oxidation alters higher-order protein structures, often inducing aggregation.
  • Oxidized products can exhibit altered pharmacokinetics, reduced biological activity, and increased immunogenicity.
  • Examples include monoclonal antibodies, insulin, growth hormone, and interferons.

Conclusions:

  • Oxidation significantly impacts the quality and efficacy of therapeutic proteins and peptides.
  • Comprehensive characterization of oxidation products is essential for drug safety and development.
  • Evaluating the biological impact of oxidation-induced changes is critical for therapeutic success.

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