PURPOSE There is an urgent need to develop effective therapies and treatment strategies to treat hypoxic tumors, which have a very poor prognosis and do not respond well to existing therapies. METHODS A novel hypoxia-targeting agent, KEMTUB012-NI2, was synthesized by conjugating a 2-nitroimidazole hypoxia-targeting moiety to a synthetic tubulysin, a very potent antimitotic. Its hypoxic select...

Recent investigations have implicated vitamin E as a possible cofactor for the oxidized diphosphopyridine nucleotide (DPN)and succinate-cytochrome c reductases of rat skeletal muscle and bovine heart muscle. It was demonstrated that added vitamin E increases the activity of the above cytochrome c reductases. Moreover, the almost complete loss of enzymatic activity resulting from isooctane extra...

One-electron reductases that reduce nitro compounds in hypoxic human tumour cells are poorly characterized, but are important for targeting hypoxia with nitroaromatic prodrugs. Fluorogenic probes with defined reductase profiles are needed to interrogate the activity of these enzymes in intact cells. In the present paper, we report a 6-nitroquinolone ester (FSL-61) as a fluorogenic probe for POR...

Most oxygenic phototrophs, including cyanobacteria, have two structurally unrelated protochlorophyllide (Pchlide) reductases in the penultimate step of chlorophyll biosynthesis. One is light-dependent Pchlide reductase (LPOR) and the other is dark-operative Pchlide reductase (DPOR), a nitrogenase-like enzyme assumed to be sensitive to oxygen. Very few studies have been conducted on how oxygen-s...

The application of biocatalysis to the synthesis of chiral molecules is one of the greenest technologies for the replacement of chemical routes due to its environmentally benign reaction conditions and unparalleled chemo-, regio- and stereoselectivities. We have been interested in searching for carbonyl reductase enzymes and assessing their substrate specificity and stereoselectivity. We now re...

Two NADPH-cytochrome P450 reductase-encoding cDNAs were isolated from an Arabidopsis cDNA library by metabolic interference in a Saccharomyces cerevisiae mutant disrupted for its endogenous cpr1 gene. ATR1 encodes a protein of 692 amino acids, while ATR2 encodes either a 712-residue protein (ATR2-1), or a 702-residue protein (ATR2-2) depending on the choice of the initiation codon. Comparative ...

Although “Prelog’s rule” and “two hydrophobic binding pockets” model have been used to predict and explain the stereoselectivity of enzymatic ketone reduction, the molecular basis of stereorecognition by carbonyl reductases has not been well understood. The stereo selectivity is not only determined by the structures of enzymes and substrates, but also affected by the reaction conditions such as...