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dc.contributor.authorHu, Lei
dc.contributor.authorJoshi, Sangeeta B.
dc.contributor.authorAndra, Kiran K.
dc.contributor.authorThakkar, Santosh V.
dc.contributor.authorVolkin, David B.
dc.contributor.authorBann, James G.
dc.contributor.authorMiddaugh, C.R.
dc.identifier.citationHu, Lei; Joshi, Sangeeta B.; Andra, Kiran K.; Thakkar, Santosh V.; Volkin, David B.; Bann, James 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, v.101 no.11 pp.4118-4128en_US
dc.descriptionClick on the DOI link to access the article (may not be free).en_US
dc.description.abstractProtective 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 78. 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.relation.ispartofseriesJournal of Pharmaceutical Sciences;v.101 no.11
dc.subjectcircular dichroismen_US
dc.subjectfluorescence spectroscopyen_US
dc.subjectphysical characterizationen_US
dc.titleComparison of the structural stability and dynamic properties of recombinant anthrax protective antigen and its 2-fluorohistidine-labeled analogueen_US

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