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 flavoprotein having a molecular weight in therange 20-60 Kilodaltons; 2) it requires either NADH or NAD(P)H or analogu es thereof as a cofactor; 3) it has a Km for NADH or NAD(P)H in the range 1-100 .mu.M; and 4) it incapable of reducing either of both nitro groups of CB 1954 and ana- logues thereof to a cytotoxic form e.g. the hydroxylamine. The sequence of o ne such nitroreductase is shown in Seq. ID No. 1. The nitroreductase maybe conjugated to a tumour targeting agent such as a monoclonal antibody and used to convert prodrugs into active antitumour agents. Such prodrugs and drugs are also provided.