Selective Oxidation of Methionine and Tryptophan Residues in a Therapeutic IgG1 Molecule

Folzer, Emilien and Diepold, Katharina and Bomans, Katrin and Finkler, Christof and Schmidt, Roland and Bulau, Patrick and Huwyler, Jörg and Mahler, Hanns-Christian and Koulov, Atanas V.. (2015) Selective Oxidation of Methionine and Tryptophan Residues in a Therapeutic IgG1 Molecule. Journal of pharmaceutical sciences, 104 (9). pp. 2824-2831.

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Official URL: http://edoc.unibas.ch/40831/

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Oxidation of methionine and tryptophan are common degradation pathways for monoclonal antibodies and present major analytical challenges in biotechnology. Generally, protein oxidation is detectable in stability and/or stressed samples (e.g., exposed to hydrogen peroxide, UV light, or metal ions). The induced chemical modifications may impact the biological activity of antibodies and may have biological consequences. However, these effects and the contribution of individual protein modifications are difficult to delineate as different amino acids are often oxidized simultaneously and accompanied by other degradants such as aggregates, especially in forced degradation studies. Here, we report a new method to obtain selective oxidation of methionine or tryptophan by using oxidation reagents combined with large excess of free tryptophan or methionine, correspondingly. More specifically, using hydrogen peroxide or tert-butyl hydroperoxide in combination with addition of free tryptophan allowed for selective oxidation of methionine. Conversely, the use of 2,2-azobis(2-amidinopropane) dihydrochloride in combination with free methionine resulted in selective tryptophan oxidation, whereas methionine oxidation was not significantly altered. This novel stress model system may prove to be valuable tool in future mechanistic studies of oxidative degradation of protein therapeutics.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmaceutical Technology (Huwyler)
UniBasel Contributors:Huwyler, Jörg
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Pharmaceutical Association
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:11 Aug 2016 06:30
Deposited On:11 Aug 2016 06:30

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