ArticlePharmaceuticals (Basel, Switzerland)2023
Site-Specific Structural Changes in Long-Term-Stressed Monoclonal Antibody Revealed with DEPC Covalent-Labeling and Quantitative Mass Spectrometry.
Article in Pharmaceuticals (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed, 3 citations in OpenAlex.
- Proteins Can Withstand More Extensive Labeling while Providing Accurate Structural Information in Covalent Labeling-Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2024Article
- "IgG's: contending with aggregating circumstances".International journal of molecular biology (Edmond, Okla.) · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Studies of structural changes in mAbs under forced stress and storage conditions are essential for the recognition of degradation hotspots, which can be further remodeled to improve the stability of the respective protein. Herein, we used diethyl pyrocarbonate (DEPC)-based covalent labeling mass spectrometry (CL-MS) to assess structural changes in a model mAb (SILuMAb). Structural changes in the heat-stressed mAb samples were confirmed at specific amino acid positions from the DEPC label mass seen in the fragment ion mass spectrum. The degree of structural change was also quantified by increased or decreased DEPC labeling at specific sites; an increase or decrease indicated an unfolded or aggregated state of the mAb, respectively. Strikingly, for heat-stressed SILuMAb samples, an aggregation-prone area was identified in the CDR region. In the case of longterm stress, the structural consequences for SILuMAb samples stored for up to two years at 2-8 °C were studied with SEC-UV and DEPC-based CL-MS. While SEC-UV analysis only indicated fragmentation of SILuMAb, DEPC-based CL-MS analysis further pinpointed the finding to structural disturbances of disulfide bonds at specific cysteines. This emphasized the utility of DEPC CL-MS for studying disulfide rearrangement. Taken together, our data suggests that DEPC CL-MS can complement more technically challenging methods in the evaluation of the structural stability of mAbs.
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Registered trials
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