Structural Evaluation of a Nitroreductase Engineered for Improved Activation of the 5-Nitroimidazole PET Probe SN33623.

Bacterial nitroreductase enzymes capable of activating imaging probes and prodrugs are valuable tools for gene-directed enzyme prodrug therapies and targeted cell ablation models. We recently engineered a nitroreductase ( NfsB F70A/F108Y) for the substantially enhanced reduction of the 5-nitroimidazole PET-capable probe, SN33623, which permits the theranostic imaging of vectors labeled with oxygen-insensitive bacterial nitroreductases. This mutant enzyme also shows improved activation of the DNA-alkylation prodrugs CB1954 and metronidazole.

Redox Properties of Ferredoxin:NADP Oxidoreductase: Potentiometric Characteristics and Reactions with Pro-Oxidant Xenobiotics.

ferredoxin:NADP oxidoreductase (FNR) is a thioredoxin reductase-type FNR whose redox properties and reactivity with nonphysiological electron acceptors have been scarcely characterized. On the basis of redox reactions with 3-acetylpyridine adenine dinucleotide phosphate, the two-electron reduction midpoint potential of the flavin adenine dinucleotide (FAD) cofactor was estimated to be -0.240 V.

The Catalysis Mechanism of Nitroreductase A, a Candidate for Gene-Directed Prodrug Therapy: Potentiometric and Substrate Specificity Studies.

nitroreductase A (NfsA) is a candidate for gene-directed prodrug cancer therapy using bioreductively activated nitroaromatic compounds (ArNO). In this work, we determined the standard redox potential of FMN of NfsA to be -215 ± 5 mV at pH 7.0.

Enzymatic Redox Properties and Cytotoxicity of Irreversible Nitroaromatic Thioredoxin Reductase Inhibitors in Mammalian Cells.

NADPH:thioredoxin reductase (TrxR) is considered a potential target for anticancer agents. Several nitroheterocyclic sulfones, such as Stattic and Tri-1, irreversibly inhibit TrxR, which presumably accounts for their antitumor activity. However, it is necessary to distinguish the roles of enzymatic redox cycling, an inherent property of nitroaromatics (ArNO), and the inhibition of TrxR in their cytotoxicity.

Modified quantum mechanical approach for the estimation of single-electron reduction potential of nitroaromatic compounds in aqueous medium.

The midpoint single-electron reduction potential of nitroaromatic compounds in aqueous medium at pH 7.0 (potential of ArNO/ArNO couple, ) frequently determines their therapeutic and/or toxic properties. However, its estimation remains a complex problem.