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Biomedical subjects

J G Cory

Publications and source records attributed to J G Cory.

At least 109 records · Page 6Linked to original sources
PubMed1976

Inhibition of transfer ribonucleic acid nucleotidyl transferase (EC 2.7.7.25) from Ehrlich tumor cells by proflavine sulfate and ethidium bromide.

Transfer RNA nucleotidyl transferase from Ehrlich tumor cells was inhibited by proflavine sulfate and ethidium bromide but not by actinomycin D, chromomycin, rifamycin SV, rifampin, daunomycin, or alpha-amanitin. Complete inhibition of nucleotidyl transferase activity was attained at a final concentration of 1 mmol/1 proflavine sulfate, while 2 mmol/1 ethidium bromide was required to completely inhibit the enzyme. CMP incorporation into tRNA was more sensitive to both proflavine sulfate and ethidium bromide than was AMP incorporation.

Acridines↗
PubMed1976

Inhibition of ribonucleotide reductase activity and nucleic acid synthesis in tumor cells by the dialdehyde derivatives of inosine (NSC 118994) and inosinic acid.

Periodate-oxidized inosine (Inox; NSC 118994) and periodate-oxidized 5'-inosinic acid (PI-IMP) were prepared and studied for their effects on ribonucleotide reductase activity in partially purified extracts from Ehrlich tumor cells and on nucleic acid synthesis in intact tumor cells in culture. Ribonucleotide reductase activity in cell-free extracts from Ehrlich tumor cells was inhibited by Inox and PI-IMP. PI-IMP was more inhibitory to the reductase activity than was Inox. Furthermore, the inhibition of ribonucleotide reductase activity by Inox and PI-IMP was greater for cytidine-5'-diphosphate reductase activity than for adenosine-5'-diphosphate reductase activity. The ribonucleotide reductase activity in cell-free extracts prepared from Ehrlich tumor cells treated with Inox or PI-IMP in culture was decreased compared with the activity in the extracts from untreated cells. Incorporation of labeled cytidine into the RNA and DNA of Ehrlich tumor cells in culture was inhibited by both Inox and PI-IMP. The conversion of cytidine to deoxycytidine nucleotides in the acid-soluble pool was likewise inhibited. These data indicate that Inox and PI-IMP inhibit the ribonucleotide reductase step as one of the sites of action of these compounds. However, the inhibition of RNA synthesis indicates that there must be additional sites of action of these nucleoside analogs.

Aldehydes↗
PubMed1975

Studies on mammalian ribonucleotide reductase inhibition by pyridoxal phosphate and the dialdehyde derivatives of adenosine, adenosine 5'-monophosphate, and adenosine 5'-triphosphate.

Ribonucleotide reductase activity in a partially purified enzyme preparation from Ehrilich tumor cells was inhibited by the dialdehyde derivatives of adenosine, 5-adenylic acid, and adenosine 5-triphosphate (prepared by the periodate oxidation of adenosine 5-adenylic acid, and adenosine 5-triphosphate). The borohydride-reduced derivative of periodate-oxidized adenosine was not inhibitory to the ribonucleotide reductase activity, showing that the aldehyde moiety was important in the inhibitory interactions of these compounds. This suggested the formation of a Schiff base between the dialdehyde derivative and an amino group (presumably, the epsilon-amino group of lysine). Pyridoxal phosphate, which is known to inhibit enzymes that have lysyl residues in the catalytic or allosteric sites, was an inhibitor of ribonucleotide reductase. Pyridoxal, pyridoxamine phosphate, pyridoxamine, and pyridoxine were not inhibitors. Borohydride reduction of the enzyme in the presence of pyridoxal phosphate produced a protein fraction that had little reductase activity remaining. The inhibition by pyridoxal phosphate was not influenced by increasing the substrate concentration (cytidine 5-diphosphate or adenosine 5-diphosphate), but was diminished by increasing the ratio of allosteric effector to pyridoxal phosphate concentrations, suggesting an interaction of pyridoxal phosphate at the regulatory site of ribonucleotide reductase. The addition of adenosine 5-triphosphate to the pyridoxal phosphate-enzyme mixture, which was subsequently treated with borohydride, partially prevented the inhibition by pyridoxal phosphate. Heat treatment of the ribonucleotide reductase enzyme preparation in the presence of pyridoxal phosphate protected the enzyme against loss of cytidine 5-diphosphate and adenosine 5-diphosphate reductase activities.

Adenosine↗
PubMed1975

Comparison of the cytidine 5'-diphosphate and adenosine 5'-diphosphate reductase activities of mammalian ribonucleotide reductase.

A comparison of the cytidine 5'-diphosphate (CDP) and adenosine 5'-diphosphate (ADP) reductase activities from Ehrlich tumor cells was made to determine if the properties of the enzyme for these substrates were the same, except for the allosteric effector. It was observed that various purification steps did not result in an enzyme fraction that had a constant ratio of CDP:ADP reductase activities. The optimal Mg2+ ion concentration for CDP reduction was 3 to 4 mM, while the optimal Mg2+ ion concentration for ADP reduction was 0.1 mM inhibited ADP reduction. CDP reduction was relatively insensitive to the presence of dimethylformamide or dimethyl sulfoxide in the reaction mixture, but ADP reduction was decreased in the presence of these two compounds. Periodate-oxidized adenosine 5'-monophosphate, on incubation with the enzyme, had a greater effect on CDP reduction but little or no effect on ADP reduction. The response of the CDP and ADP reductase activities to the same negative effector was essentially the same. Both CDP and ADP reductions showed similar decreases in the presence of various concentrations of deoxyadenosine 5'-triphosphate. These data suggest that the Ehrlich tumor cell reductase enzyme system could consist of at least two different enzymes that may be regulated by the same allosteric protein.

Adenosine Diphosphate↗