Roy B, Lepoivre M, Decout J L, Lhomme J, Fontecave M
Laboratoire d'Etudes Dynamiques et Structurales de la Sélectivité, URA CNRS 332, Université Joseph Fourier, Grenoble, France.
Biochem Biophys Res Commun. 1992 Aug 31;187(1):432-7. doi: 10.1016/s0006-291x(05)81511-6.
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.
核糖核苷酸还原酶抑制剂是潜在的抗增殖剂，因为它们会使细胞缺乏DNA前体。在碱基部分带有叠氮基的底物核苷类似物，通过抑制胸苷掺入DNA来测定，显示出很强的细胞生长抑制特性。一种化合物，8-叠氮腺苷，可抑制癌细胞胞质提取物中CDP的还原。相应的二磷酸作为核糖核苷酸还原酶的底物，而三磷酸是一种变构效应剂。
