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Structure and function of purified monoclonal antibody dimers induced by different stress conditions

Paul, Rajsekhar and Graff-Meyer, Alexandra and Stahlberg, Henning and Lauer, Matthias E. and Rufer, Arne C. and Beck, Hermann and Briguet, Alexandre and Schnaible, Volker and Buckel, Thomas and Boeckle, Sabine. (2012) Structure and function of purified monoclonal antibody dimers induced by different stress conditions. Pharmaceutical research, Vol. 29, H. 8. pp. 2047-2059.

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Official URL: http://edoc.unibas.ch/dok/A6056072

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Abstract

To investigate structure and function of different monoclonal antibody (MAb) dimers.; MAb dimers were induced by process-related, low pH and UV light stress. Dimers were isolated and purified by chromatography and extensively characterized by biochemical, structural and functional methods.; Highly purified dimer forms were obtained which enabled detailed characterization. Dimers induced by process stress were associated by a single non-covalent interaction site between two Fab domains in a characteristic "bone-like" structure observed in Transmission Electron Microscopy (TEM). These dimers showed reduced potency and antigen binding affinity. Low pH stress generated more stable but also non-covalently associated dimers without chemical alterations in a typical "closed" conformation according to TEM. These dimer species were more compact and more hydrophobic as dimers induced by process stress. They showed bioactivity and antigen binding affinity similar to the native monomer. Light-induced dimers, exhibiting various different conformations, were the most stable dimers with various chemical modifications leading to a broad range in size, charge and hydrophobicity. These dimers fully lost bioactivity and antigen binding affinity.; The use of highly purified MAb dimers and a panel of characterizations methods enabled to obtain a clear picture about molecular architecture and function of dimers.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Stahlberg)
UniBasel Contributors:Stahlberg, Henning
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Plenum Press
ISSN:0724-8741
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Feb 2013 08:46
Deposited On:01 Feb 2013 08:41

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