Domain ii mutants of anthrax lethal factor

Details Domain ii mutants of anthrax lethal factor Domain ii mutants of anthrax lethal factor

C - Chemistry, Metallurgy

07

K

C07K 14/32 (2006.01)

Patent

CA 2580969

A series of mutants of Anthrax lethal factor (LF) are disclosed which define a conformational epitope or region of the molecule that interacts with the LF target, the MEK enzyme. Such mutants or variants, and nucleic acids encoding them are disclosed. The knowledge of such binding, separate from recognition of MEK by the protease active site of LF, serves as the basis for novel screening assays for discovery of inhibitors of this additional form of LF-MEK binding which is necessary for ultimate proteolysis and toxicity. The nontoxic LF mutants are useful as immunogenic compositions for generating antibodies and a state of immunity specific for the LF component of a B. anthracis infection or exposure otherwise to the anthrax lethal toxin.

L'invention concerne une série de mutants du facteur létal de l'anthrax (LF) qui définissent un épitope conformationnel ou une région de la molécule qui interagit avec la cible de LF, l'enzyme MEK. L'invention concerne lesdits mutants ou variants, ainsi que des acides nucléiques codant pour ces derniers. La connaissance de ladite liaison, séparée de la reconnaissance de MEK par le site actif de la protéase de LF, sert de base à de nouveaux essais de criblage permettant la découverte d'inhibiteurs de ladite forme additionnelle de liaison de LF-MEK qui est nécessaire pour la protéolyse et la toxicité finales. Les mutants de LF non toxiques sont utiles en tant que compositions immunogènes permettant de générer des anticorps et un état d'immunité spécifique pour le composant LF d'une infection par B. anthracis ou différemment une exposition à la toxine létale de l'anthrax.

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