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• W2065520294 endingPage "182" @default.
• W2065520294 startingPage "167" @default.
• W2065520294 abstract "The monophosphates of the exocyclic amino ribonucleosides, 4-amino- and 4-methoxy-8-(D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine, are potent and specific inhibitors of human erythrocyte and B-lymphoblast PRPP synthetase. The inhibition by MRPP monophosphate is competitive (Ki = 35 microM with the PRPP synthetase cofactor, Pi (Km = 2 mM). The nucleosides are phosphorylated to the active metabolite by adenosine kinase and these nucleoside monophosphates accumulate in the cell. beta-ARPP is a substrate, albeit poor, for adenosine deaminase and solutions of the beta-anomer of this nucleoside and its monophosphate anomerize over time to give alpha- and beta-mixtures. beta-MRPP is more resistant to adenosine deaminase and anomerization of the nucleoside and its monophosphate is negligible. The effect of treatment of cells with the nucleosides is a time-dependent and nearly universal reduction in the nucleotide content which appears to result from a reduction in the availability of PRPP for dependent metabolic pathways. In studies with the WI-L2 lymphoblasts, some of these pathways, de novo and salvage (hypoxanthine and guanine) synthesis of purine nucleotides, are more sensitive to a restriction of PRPP availability than others, i.e. de novo pyrimidine synthesis. The nucleosides have shown promise as therapeutic agents in a mouse leukemia evaluation system but may also have future use in unravelling the complex regulation of PRPP synthetase and the dependent nucleotide synthesis pathways." @default.
• W2065520294 created "2016-06-24" @default.
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• W2065520294 date "1989-01-01" @default.
• W2065520294 modified "2023-10-18" @default.
• W2065520294 title "Potent and specific inhibitors of mammalian phosphoribosylpyrophosphate (PRPP) synthetase" @default.
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• W2065520294 doi "https://doi.org/10.1016/0065-2571(89)90070-8" @default.
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