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Freezing-induced perturbation of tertiary structure of a monoclonal antibody.


ABSTRACT: We studied the effects of pH and solution additives on freezing-induced perturbations in the tertiary structure of a monoclonal antibody (mAb) by intrinsic tryptophan fluorescence spectroscopy. In general, freezing caused perturbations in the tertiary structure of the mAb, which were reversible or irreversible depending on the pH or excipients present in the formulation. Protein aggregation occurred in freeze-thawed samples in which perturbations of the tertiary structure were observed, but the levels of protein aggregates formed were not proportional to the degree of structural perturbation. Protein aggregation also occurred in freeze-thawed samples without obvious structural perturbations, most likely because of freeze concentration of protein and salts, and thus reduced protein colloidal stability. Therefore, freezing-induced protein aggregation may or may not first involve the perturbation of its native structure, followed by the assembly processes to form aggregates. Depending on the solution conditions, either step can be rate limiting. Finally, this study demonstrates the potential of fluorescence spectroscopy as a valuable tool for screening therapeutic protein formulations subjected to freeze-thaw stress.

SUBMITTER: Liu L 

PROVIDER: S-EPMC4069245 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Freezing-induced perturbation of tertiary structure of a monoclonal antibody.

Liu Lu L   Braun Latoya Jones LJ   Wang Wei W   Randolph Theodore W TW   Carpenter John F JF  

Journal of pharmaceutical sciences 20140515 7


We studied the effects of pH and solution additives on freezing-induced perturbations in the tertiary structure of a monoclonal antibody (mAb) by intrinsic tryptophan fluorescence spectroscopy. In general, freezing caused perturbations in the tertiary structure of the mAb, which were reversible or irreversible depending on the pH or excipients present in the formulation. Protein aggregation occurred in freeze-thawed samples in which perturbations of the tertiary structure were observed, but the  ...[more]

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