Protective antigen having fluorinated histidine residues

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Issue Date
2010-06-08
Authors
Bann, James G.
Advisor
Citation

Bann, James G., inventor. Wichita State University, assignee. Protective antigen having fluorinated histidine residues. Unites States patent: US 7,731,979. 2010, Jun 8.

Abstract

The unnatural amino acid analogue 2-fluorohistidine (2-FHis) was incorporated into protective antigen to produce a protein which resists protonation at physiological pH by reducing the side-chain pKa. The protein structure was unperturbed by the incorporation of fluorinated histidine residues, and the heptameric (2-FHisPA.sub.63).sub.7 could form ion conducting channels, and bind to the PA-binding domain of LF (LF.sub.N), but translocation of LF.sub.N in planar lipid bilayers was blocked. Further, while (2-FHisPA.sub.63).sub.7 could bind to host cells and in vitro to the host cellular receptor, pore formation in the presence of the receptor was blocked, and LF.sub.N-DTA mediated cytotoxicity in CHO-K1 cells was blocked. The modified PA is useful as both a vaccine and an antitoxin, providing epitopes for the production of antibodies against PA, but preventing key steps in pathogenesis (pore formation, translocation).

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Description
WSU inventor: James G. Bann, Dept. of Chemistry, College of Liberal Arts and Sciences
Appl. no.: 11/939,249 filed Nov. 13, 2007. U.S. Patent 7,731,979 granted Jun 8, 2010.
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