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dc.contributor.authorAlsenaidy, Mohammad A.
dc.contributor.authorKim, Jae Hyun
dc.contributor.authorMajumdar, Ranajoy
dc.contributor.authorWeis, David D.
dc.contributor.authorJoshi, Sangeeta B.
dc.contributor.authorTolbert, Thomas J.
dc.contributor.authorMiddaugh, C. Russell
dc.contributor.authorVolkin, David B.
dc.date.accessioned2017-04-25T19:03:41Z
dc.date.available2017-04-25T19:03:41Z
dc.date.issued2013-11
dc.identifier.citationAlsenaidy, M. A., Kim, J. H., Majumdar, R., Weis, D. D., Joshi, S. B., Tolbert, T. J., … Volkin, D. B. (2013). High-Throughput Biophysical Analysis and Data Visualization of Conformational Stability of an IgG1 Monoclonal Antibody (mAb) After Deglycosylation. Journal of Pharmaceutical Sciences, 102(11), 10.1002/jps.23730. http://doi.org/10.1002/jps.23730en_US
dc.identifier.urihttp://hdl.handle.net/1808/23769
dc.description.abstractThe structural integrity and conformational stability of an IgG1 monoclonal antibody (mAb), after partial and complete enzymatic removal of the N-linked Fc glycan, was compared to the untreated mAb over a wide range of temperature (10° to 90°C) and solution pH (3 to 8) using circular dichroism, fluorescence spectroscopy, and static light scattering combined with data visualization employing empirical phase diagrams (EPDs). Subtle to larger stability differences between the different glycoforms were observed. Improved detection of physical stability differences was then demonstrated over narrower pH range (4.0-6.0) using smaller temperature increments, especially when combined with an alternative data visualization method (radar plots). Differential scanning calorimetry and differential scanning fluorimetry were then utilized and also showed an improved ability to detect differences in mAb glycoform physical stability. Based on these results, a two step methodology was used in which mAb glycoform conformational stability is first screened with a wide variety of instruments and environmental stresses, followed by a second evaluation with optimally sensitive experimental conditions, analytical techniques and data visualization methods. With this approach, high-throughput biophysical analysis to assess relatively subtle conformational stability differences in protein glycoforms is demonstrated.en_US
dc.publisherElsevieren_US
dc.rightsThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.subjectGlycosylationen_US
dc.subjectMonoclonal Antibodyen_US
dc.subjectStabilityen_US
dc.subjectStructureen_US
dc.subjectConformationen_US
dc.subjectBiophysicalen_US
dc.subjectFormulationen_US
dc.titleHigh-Throughput Biophysical Analysis and Data Visualization of Conformational Stability of an IgG1 Monoclonal Antibody (mAb) After Deglycosylationen_US
dc.typeArticleen_US
kusw.kuauthorAlsenaidy, Mohammad A.
kusw.kuauthorKim, Jae Hyun
kusw.kuauthorMajumdar, Ranajoy
kusw.kuauthorWeis, David D.
kusw.kuauthorJoshi, Sangeeta B.
kusw.kuauthorTolbert, Thomas J.
kusw.kuauthorMiddaugh, C. Russell
kusw.kuauthorVolkin, David B.
kusw.kudepartmentPharmaceutical Chemistryen_US
dc.identifier.doi10.1002/jps.23730en_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC3832129en_US
dc.rights.accessrightsopenAccess


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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.