BACTERIAL NITROREDUCTASE FOR THE REDUCTION OF CB 1954 AND ANALOGUES THEREOF TO A CYTOTOXIC FORM

摘要

The invention provides a nitroreductase, obtainable from a bacterium havingthe following characteristics as exemplifiedby examples isolated from Escherichia coli B and Bacillus amyloliquifaciens:1) it is flavoprotein having a molecular weight intherange 20-60 Kilodaltons; 2) it requires either NADH or NAD(P)H or analoguesthereof as a cofactor; 3) it has a Km forNADH or NAD(P)H in the range 1-100 µM; and 4) it incapable of reducingeither of both nitro groups of CB 1954 and ana-logues thereof to a cytotoxic form e.g. the hydroxylamine. The sequence of onesuch nitroreductase is shown in Seq. ID No. 1.The nitroreductase maybe conjugated to a tumour targeting agent such as amonoclonal antibody and used to convert prodrugsinto active antitumour agents. Such prodrugs and drugs are also provided.