Protective antigen having fluorinated histidine residues

Details Protective antigen having fluorinated histidine residues Protective antigen having fluorinated histidine residues

2007-11-13

2010-06-08

Ford, Vanessa L. (Department: 1645)

Drug, bio-affecting and body treating compositions

Antigen, epitope, or other immunospecific immunoeffector

Bacterium or component thereof or substance produced by said...

C424S001890, C424S184100, C424S234100, C424S236100, C514S002600

Reexamination Certificate

active

07731979

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)7could form ion conducting channels, and bind to the PA-binding domain of LF (LFN), but translocation of LFNin planar lipid bilayers was blocked. Further, while (2-FHisPA63)7could 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).

REFERENCES:
Zhou et al (The 40th Midwest Region Meeting, BIOMED Poster Session, Oct. 26-29, 2005, acs.confex.com).
Zhou (SOAR at Wichita State University Libraries), http://hdl.handle.net/10057/560, issued date Jul. 2006).
Bowie et al (Science, 1990, 257:1306-1310).
Zhou, Influence of Fluorohistidine on Pore Formation in the Anthrax Protective Antigen, (SOAR at Wichita State University Libraries), http://hdl.handle.net/10057/560, issued date Jul. 2006 publically available Jul. 2007).
Conference Summary, (Emerging Infectious Diseases, vol. 8, No. 2, Feb. 2002, p. 222-225).
Bann,Probing the role of histidine in the anthrax toxin protective antigen with 2-fluoro-histidine, PowerPoint Presentation, 3rdAnnual RCE National meeting in New York City (Mar. 27, 2006).

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