Protective antigen having fluorinated histidine residues
US7731979B2 · kind B2 · utility
Assignee
Inventor
Key dates
| Filing date | Nov 13, 2007 |
| Grant date | Jun 8, 2010 |
| Priority date | — |
| Expiry date | Dec 1, 2027 |
Classification
- Technology area (CPC A)Human Necessities
- CPC primaryA61K39/00
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
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).
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.