abstract |
The present invention relates to polypeptides and proteins having nitroreductase activity. The invention also relates to DNA and genes encodin g 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 achie ve catalysis of CB1954 into its cytotoxic derivative in a site-directed manner, such as by Directed-Enzyme Prodrug Therapy (DEPT). |