Identification of Non-nucleoside Human Ribonucleotide Reductase Modulators

Nucleoside 5'-diphosphates as effectors of mammalian ribonucleotide reductase.

It was found that nucleoside 5'-diphosphates could serve as effectors of ribonucleotide reductase. ADP was an activator of CDP reduction; ADP reduction was activated by dGDP; GDP reduction was activated by dTDP. Conversely, dADP inhibited the reduction of CDP, UDP, GDP, and ADP; dGDP inhibited UDP and GDP reductions; and dTDP inhibited UDP reduction. The inhibition of UDP reduction by dADP, dTD...

Substrate specificity of human ribonucleotide reductase from Molt-4F cells.

Nucleoside triphosphates were examined as the activator for various nucleoside diphosphate reductions catalyzed by a highly purified ribonucleotide reductase obtained from Molt-4F cultured human cells. It was found that cytidine 5'-diphosphate and uridine diphosphate reductions are activated by adenosine 5'-triphosphate with apparent Ka's of 0.63 +/- 0.03 (S.E.) and 1.25 +/- 0.10 mM, respective...

Therapeutic Discovery Evaluating the Therapeutic Potential of a Non-Natural Nucleotide That Inhibits Human Ribonucleotide Reductase

Human ribonucleotide reductase (hRR) is the key enzyme involved in de novo dNTP synthesis and thus represents an important therapeutic target against hyperproliferative diseases, most notably cancer. The purpose of this study was to evaluate the ability of non-natural indolyl-20-deoxynucleoside triphosphates to inhibit the activity of hRR. The structural similarities of these analogues with dAT...

Evaluating the therapeutic potential of a non-natural nucleotide that inhibits human ribonucleotide reductase.

Human ribonucleotide reductase (hRR) is the key enzyme involved in de novo dNTP synthesis and thus represents an important therapeutic target against hyperproliferative diseases, most notably cancer. The purpose of this study was to evaluate the ability of non-natural indolyl-2'-deoxynucleoside triphosphates to inhibit the activity of hRR. The structural similarities of these analogues with dAT...

Ribonucleotide reductase in developing brain.