Synthetic Nucleotide Analogs are Used in Chemotherapy
المؤلف:
Peter J. Kennelly, Kathleen M. Botham, Owen P. McGuinness, Victor W. Rodwell, P. Anthony Weil
المصدر:
Harpers Illustrated Biochemistry
الجزء والصفحة:
32nd edition.p334-335
2025-08-30
347
Synthetic analogs of purines, pyrimidines, nucleosides, and nucleotides modified in the heterocyclic ring or in the sugar moiety have numerous applications in clinical medicine. Their toxic effects reflect either inhibition of enzymes essential for nucleic acid synthesis or their incorporation into nucleic acids with resulting disruption of base pairing. Oncologists employ 5-fluoro- or 5-iodouracil, 3-deoxyuridine, 6-thioguanine and 6-mercaptopurine, 5- or 6-azauridine, 5- or 6-azacytidine, and 8-azaguanine (Figure 1), which are incorporated into DNA prior to cell division. The purine analog allopurinol, used in treatment of hyperuricemia and gout, inhibits purine biosynthesis and xanthine oxidase activity. Cytarabine is used in chemotherapy of cancer, and azathioprine, which is catabolized to 6-mercaptopurine, is employed during organ trans plantation to suppress immunologic rejection (Figure2).
Fig1. Selected synthetic pyrimidine and purine analogs.
Fig2. Cytarabine and azathioprine.
Non-Hydrolyzable Nucleoside Triphosphate Analogs Serve as Research Tools
Synthetic, non-hydrolyzable analogs of nucleoside triphosphates (Figure 3) allow investigators to distinguish the effects of nucleotides due to phosphoryl transfer from effects mediated by occupancy of allosteric nucleotide-binding sites on regulated enzymes.
Fig3. synthetic derivatives of nucleoside triphosphates incapable of undergoing hydrolytic release of the terminal phosphoryl group. (Pu/Py, a purine or pyrimidine base; R, ribose or deoxyribose.) Shown are the parent (hydrolyzable) nucleoside triphosphate (top) and the unhydrolyzable β-methylene (center) and γ-imino derivatives (bottom).
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