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Gas-phase unfolding assay rapidly predicts structure-function relationships in engineered antibodies with tuned flexibilities

Abstract:
Human (h)IgG2 monoclonal antibodies (mAbs) are potent agonists due, in part, to their ability to undergo disulfide shuffling within their hinge regions. Herein, we describe a rapid, sensitive, collision-induced unfolding (CIU) assay that possesses a predictive relationship between gas-phase protein unfolding and agonism in hIgG2 variants. Furthermore, our results highlight the significance of hinge engineering in tuning mAb structure-function relationships for the development of future biotherapeutics.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-026-75137-y

Authors

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Role:
Author
ORCID:
0000-0002-3969-7381
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Role:
Author
ORCID:
0000-0002-9453-3419
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Role:
Author
ORCID:
0000-0003-0093-0921
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Institution:
University of Oxford
Role:
Author
ORCID:
0000-0003-4535-5932


Publisher:
Nature Research
Journal:
Nature Communications More from this journal
Publication date:
2026-06-29
Acceptance date:
2026-06-24
DOI:
EISSN:
2041-1723
ISSN:
2041-1723


Language:
English
Keywords:
Pubs id:
2442574
Local pid:
pubs:2442574
Source identifiers:
W7166577412
Deposit date:
2026-07-09
ARK identifier:
This ORA record was generated from metadata provided by an external service. It has not been edited by the ORA Team.

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