Bacterial nitroreductase for the reduction of cb 1954 and...

Details Bacterial nitroreductase for the reduction of cb 1954 and... Bacterial nitroreductase for the reduction of cb 1954 and...

C - Chemistry, Metallurgy

12

N

C12N 15/53 (2006.01) A61K 31/00 (2006.01) A61K 47/48 (2006.01) C07C 219/34 (2006.01) C07C 271/18 (2006.01) C07C 271/28 (2006.01) C07D 203/14 (2006.01) C07D 487/04 (2006.01) C07D 487/14 (2006.01) C07H 15/252 (2006.01) C07H 19/048 (2006.01) C07K 7/06 (2006.01) C07K 16/40 (2006.01) C12N 9/02 (2006.01) C12N 11/00 (2006.01) C12P 17/10 (2006.01) C12P 21/08 (2006.01) G01N 33/554 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2122036

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 analogues thereof as a cofactor; 3) it has a Km for NADH or NAD(P)H in the range 1-100 µM; 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 one 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.

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