Site-specific tryptophan oxidation induced by autocatalytic reaction of polysorbate 20 in protein formulation
Pharmaceutical Research, ISSN: 0724-8741, Vol: 28, Issue: 10, Page: 2543-2555
2011
- 65Citations
- 71Captures
Metric Options: CountsSelecting the 1-year or 3-year option will change the metrics count to percentiles, illustrating how an article or review compares to other articles or reviews within the selected time period in the same journal. Selecting the 1-year option compares the metrics against other articles/reviews that were also published in the same calendar year. Selecting the 3-year option compares the metrics against other articles/reviews that were also published in the same calendar year plus the two years prior.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Metrics Details
- Citations65
- Citation Indexes63
- 63
- CrossRef56
- Patent Family Citations1
- Patent Families1
- Policy Citations1
- Policy Citation1
- Captures71
- Readers71
- 71
Article Description
Purpose: Tryptophan (Trp) oxidation leading to atypical degradation of a protein (Fab) formulated with polysorbate 20 (PS20) was investigated. Such atypical Trp oxidation was discussed in relation to a kinetic model that involves initiation of oxidizing free radical through an autocatalytic reaction. Methods: Ion-exchange chromatography and peptide mapping were used to determine Trp oxidation. Peroxides in PS20 and free radicals in Fab samples were detected by fluorometric assay and electron paramagnetic resonance (EPR), respectively. Results: PS20 with increased peroxides level led to degradation of Fab stored at 30°C. Degradation was characterized as Trp50 oxidation, which was not observed in a Fab variant where His31 was replaced. EPR peaks related to known spin adducts of 5,5 dimethylpyrroline N-oxide were detected in Fab exhibiting Trp oxidation, indicating free radicals were present. Trp oxidation of Fab observed in several drug product lots with different degradation rates fits an autocatalytic reaction model that involves free radicals. EDTA, catalase, and free tryptophan prevented oxidation. Conclusions: A metal-binding amino acid, His31, was responsible for Trp50 oxidation of Fab induced by peroxides in PS20 present in the protein formulation. Oxidation was induced by autocatalytic degradation of PS20 and could be inhibited by antioxidants. © 2011 Springer Science+Business Media, LLC.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=80054773616&origin=inward; http://dx.doi.org/10.1007/s11095-011-0482-x; http://www.ncbi.nlm.nih.gov/pubmed/21656082; http://link.springer.com/10.1007/s11095-011-0482-x; https://dx.doi.org/10.1007/s11095-011-0482-x; https://link.springer.com/article/10.1007/s11095-011-0482-x; http://www.springerlink.com/index/10.1007/s11095-011-0482-x; http://www.springerlink.com/index/pdf/10.1007/s11095-011-0482-x
Springer Science and Business Media LLC
Provide Feedback
Have ideas for a new metric? Would you like to see something else here?Let us know