C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 9/02 (2006.01) A61K 35/00 (2006.01) C12N 15/52 (2006.01) A61K 38/00 (2006.01) A61K 48/00 (2006.01)
Patent
CA 2362523
The present invention relates to polypeptides and proteins having nitroreductase activity. The invention also relates to DNA and genes encoding these nitroreductases, and to methods of obtaining such enzymes, DNA and genes. In a particularly preferred aspect, the nitroreductase enzymes demonstrate preferential catalytic conversion of the alkylating agent CB1954 into its highly cytotoxic 4-hydroxylamine (4HX) derivative, this derivative demonstrating anticarcinoma properties. Accordingly, the catalytic activity of the nitroreductase enzymes of the present invention may be employed to achieve catalysis of CB1954 into its cytotoxic derivative in a site-directed manner, such as by Directed-Enzyme Prodrug Therapy (DEPT).
L'invention concerne des polypeptides et des protéines possédant une activité de nitroréductase. L'invention concerne aussi des ADN et des gènes codant pour ces nitroréductases ainsi que des procédés d'obtention de ces enzymes, ADN et gènes. Dans un mode de réalisation particulièrement préféré, les enzymes de nitroréductase manifestent une conversion catalytique de l'agent d'alkylation CB1954 en son dérivé hautement cytotoxique 4-hydroxylamine (4HX), ledit dérivé manifestant des propriétés anticarcinomiques; de ce fait, l'activité catalytique des enzymes de nitroréductase de la présente invention peut s'utiliser pour effectuer la conversion catalytique de CB1954 en son dérivé cytotoxique selon un procédé agissant sur le site tel que la thérapie par promédicaments à enzymes dirigées (DEPT).
Anlezark Gill
Minton Nigel
Vaughan Thomas
Goudreau Gage Dubuc
Health Protection Agency
Microbiological Research Authority
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