Comparison of the Structural Stability and Dynamic Properties of Recombinant Anthrax Protective Antigen and its 2- Fluorohistidine Labeled Analogue
dc.contributor.author | Hu, Lei | |
dc.contributor.author | Joshi, Sangeeta B. | |
dc.contributor.author | Andra, Kiran K. | |
dc.contributor.author | Thakkar, Santosh V. | |
dc.contributor.author | Volkin, David B. | |
dc.contributor.author | Bann, James G. | |
dc.contributor.author | Middaugh, C. Russell | |
dc.date.accessioned | 2017-04-19T18:47:56Z | |
dc.date.available | 2017-04-19T18:47:56Z | |
dc.date.issued | 2012-11 | |
dc.identifier.citation | Hu, L., Joshi, S. B., Andra, K. K., Thakkar, S. V., Volkin, D. B., Bann, J. G., & Middaugh, C. R. (2012). Comparison of the Structural Stability and Dynamic Properties of Recombinant Anthrax Protective Antigen and its 2-Fluorohistidine Labeled Analogue. Journal of Pharmaceutical Sciences, 101(11), 4118–4128. http://doi.org/10.1002/jps.23294 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23740 | |
dc.description.abstract | Protective antigen (PA) is the primary protein antigenic component of both the currently used anthrax vaccine and related recombinant vaccines under development. An analogue of recombinant PA (2-FHis rPA) has been recently shown to block the key steps of pore formation in the process of inducing cytotoxicity in cells, and thus can potentially be used as an antitoxin or a vaccine. This rPA analogue was produced by fermentation to incorporate the unnatural amino acid 2-fluorohistidine (2-FHis). In this study, the effects of 2-FHis labeling on rPA antigen’s conformational stability and dynamic properties were investigated by various biophysical techniques. Temperature/pH stability profiles of rPA and 2-FHis rPA were analyzed by the empirical phase diagram (EPD) approach, and physical stability differences between them were identified. Results showed that rPA and 2-FHis rPA had similar stability at pH 7–8. With decreasing solution pH, however, 2-FHis rPA was found to be more stable. Dynamic sensitive measurements of the two proteins at pH 5 found that 2-FHis rPA was more dynamic and/or differentially hydrated under acidic pH conditions. The biophysical characterization and stability data provide information useful for the potential development of 2-FHis rPA as a more stable rPA vaccine candidate. | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | 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. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.subject | Circular dichroism | en_US |
dc.subject | Flourescence spectroscopy | en_US |
dc.subject | Physical characterization | en_US |
dc.subject | Stability | en_US |
dc.subject | Vaccines | en_US |
dc.title | Comparison of the Structural Stability and Dynamic Properties of Recombinant Anthrax Protective Antigen and its 2- Fluorohistidine Labeled Analogue | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Hu, Lei | |
kusw.kuauthor | Joshi, Sangeeta B. | |
kusw.kuauthor | Andra, Kiran K. | |
kusw.kuauthor | Thakkar, Santosh V. | |
kusw.kuauthor | Volkin, David B. | |
kusw.kuauthor | Bann, James G. | |
kusw.kuauthor | Middaugh, C. Russell | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
kusw.kudepartment | Chemistry | en_US |
kusw.kudepartment | Macromolecule and Vaccine Stabilization Center | en_US |
dc.identifier.doi | 10.1002/jps.23294 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess |
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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.