Bacterial nitroreductase for the reduction of CB 1954 and analogues thereof to a cytotoxic form

Abstract

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 flavoprotein having a molecular weight in the range of 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 of 1-100 .mu.M; and 4) it is capable of reducing either or both nitro groups of CB1954 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 antitumor agents. Such prodrugs and drugs are also provided.

Dependencies are inferred from the claim text.