8-Azidoadenosine and ribonucleotide reductase.
Inhibitors of ribonucleotide reductase are potential antiproliferative agents, since they deplete cells from DNA precursors. Substrate nucleoside analogues, carrying azido groups at the base moiety, are shown to have strong cytostatic properties, as measured by the inhibition of the incorporation of thymidine into DNA. One compound, 8-azidoadenosine, inhibits CDP reduction in cytosolic extracts from cancer cells. The corresponding diphosphate behaves as a substrate for ribonucleotide reductase while the triphosphate is an allosteric effector.
Roy
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B
Laboratoire d'Etudes Dynamiques et Structurales de la Sélectivité, URA CNRS 332, Université Joseph Fourier, Grenoble, France.
Lepoivre
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M
Decout
J L
JL
Lhomme
J
J
Fontecave
M
M
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000494:Allosteric Regulation; D000818:Animals; D001386:Azides / Q000378:metabolism / Q000494:pharmacology*; D003565:Cytidine Diphosphate / Q000378:metabolism; D051379:Mice; D009249:NADP / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D001386:Azides; C012760:8-azidoadenosine; D009249:NADP; C017040:8-azidoadenosine 5'-triphosphate; D000244:Adenosine Diphosphate; D003565:Cytidine Diphosphate; D000255:Adenosine Triphosphate; D012264:Ribonucleotide Reductases; C021622:8-azidoadenosine diphosphate; D000241:Adenosine