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Protective antigen having fluorinated histidine residues
Bann, James G.
Bann, James G.
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Bann, James G.
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2009-05-14
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Bann, J.G., inventor; Wichita State University, assignee. Protective antigen having fluorinated histidine residues. Protective antigen having fluorinated histidine residues. United States patent US 20090123458 A1. 2009, May 14.
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-FHisPA63)7 could form ion conducting channels, and bind to the PA-binding domain of LF (LFN), but translocation of LFN in planar lipid bilayers was blocked. Further, while (2-FHisPA63)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 LFN-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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WSU inventors: James G. Bann, Dept. of Chemistry, Fairmount College of Liberal Arts and Sciences
Application No: 11/939,249 filed November 13, 2007. Patent No: US 20090123458 A1 granted May 14, 2009.
Application No: 11/939,249 filed November 13, 2007. Patent No: US 20090123458 A1 granted May 14, 2009.
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United States Patent and Trademark Office
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Status: Expired
Patent Expired Due to NonPayment of Maintenance Fees Under 37 CFR 1.362 07/11/2022
Patent Expired Due to NonPayment of Maintenance Fees Under 37 CFR 1.362 07/11/2022