Testing double mutants of the enzyme nitroreductase for enhanced cell sensitisation to prodrugs: effects of combining beneficial single mutations.

doi:10.1016/j.bcp.2009.07.025

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Article

Testing double mutants of the enzyme nitroreductase for enhanced cell sensitisation to prodrugs: effects of combining beneficial single mutations.

Biochemical pharmacology - 15 Jan 2010

Jaberipour Mansooreh, Vass Simon O, Guise Christopher P, Grove Jane I, Knox Richard J, Hu Longqin, Hyde Eva I, Searle Peter F

Abstract excerpt

Prodrug activation gene therapy for cancer involves expressing prodrug-activating enzymes in tumour cells, so they can be selectively killed by systemically administered prodrug. For example, Escherichia colinfsB nitroreductase (E.C. 1.6.99.7)(NTR), sensitises cells to the prodrug CB1954 (5-[aziridin-1-yl]-2,4-dinitrobenzamide), which it converts to a potent DNA-crosslinking agent. However, low catalytic...

Topics

Animals
Base Sequence
Blotting, Western
DNA Primers
Humans
Mice
Mutation
Nitroreductases
Prodrugs

Source

Open in PubMed

Identifiers

PMID: 19665450
DOI: 10.1016/j.bcp.2009.07.025

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