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 having the following characteristics as exemplified by examples isolated from Escherichia coli B and Bacillus amyloliquifaciens: 1. It is a flavoprotein having a molecular weight in the range 20-60 Kilodaltons; 2. It requires either NADH or NAD(P)H or analogues thereof as a cofactor; 3. It has a Km for NADH or NAD(P)H in the range 1-100<0>M; and 4. It is capable of reducing either or both nitro groups of CB 1954 and analogues thereof to a cytotoxic form e.g. the hydroxylamine. The sequence of one such nitroreductase is shown in Seq. ID No.1. The nitroreductase may be conjugated to a tumor targeting agent such as a monoclonal antibody and used to convert prodrugs into active antitumour agents. Such prodrugs and drugs are also provided.