A novel nitroreductase and therapeutic uses therefor

A - Human Necessities – 61 – K

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Details

A61K 39/395 (2006.01) A61K 31/04 (2006.01) A61K 31/05 (2006.01) A61K 31/06 (2006.01) A61K 45/06 (2006.01) A61K 47/48 (2006.01) C07H 21/04 (2006.01) C07K 14/205 (2006.01) C12N 1/21 (2006.01) C12N 9/02 (2006.01) C12N 9/06 (2006.01) C12N 11/02 (2006.01)

Patent

CA 2325050

In accordance with the present invention, the gene responsible for metronidazole sensitivity in H. pylori has been identified. Mutational inactivation of the gene, which encodes an oxygen-insensitive NADPH nitroreductase, referred to herein as rdxA (designated HP0954 in the entire genome sequence) (Tomb et al., 1997) is the cause of naturally acquired MtzR in H. pylori. In accordance with one embodiment of the present invention, there is provided a method of employing RdxA and related compounds, optionally in conjunction with targeting compounds, to convert nitroaromatic compounds to cytotoxins for use in selectively killing or inhibiting the growth of target cell populations. In accordance with another aspect of the present invention, there is provided a method of employing RdxA and related compounds in order to convert nitroaromatic compounds to cytotoxins for use in selecting against cells expressing rdxA.

Selon la présente invention, le gène responsable de la sensibilité au métronidazole chez H. pylori a été identifié. L'inactivation mutationnelle du gène, qui code pour une NADPH nitroréductase insensible à l'oxygène, appelée ici RdxA (désignée par HP0954 dans la séquence du génome entier) (Tomb et al.,1997), est la cause de Mtz?R¿ naturellement acquis dans H. pylori. Selon une des réalisations, la présente invention concerne un procédé d'utilisation de RdxA et de composés associés, éventuellement conjointement avec des composés de ciblage, destiné à convertir des composés aromatiques nitrés en cytotoxines pour les utiliser dans la destruction sélective ou l'inhibition de croissance de populations de cellules cibles. Selon une autre réalisation, la présente invention concerne un procédé d'utilisation de RdxA et de composés associés destiné à convertir des composés aromatiques nitrés en cytotoxines pour les utiliser dans l'élimination, par sélection, des cellules qui expriment RdxA.

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