Synthetic Nucleotide Analogs Are Used In Chemotherapy

Synthetic analogs of purines, pyrimidines, nucleosides, and nucleotides altered in either the heterocyclic ring or 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-mer-captopurine, 5- or 6-azauridine, 5- or 6-azacytidine, and 8-azaguanine (Figure 33-12), 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. Finally, azathioprine, which is catabolized to 6-mercap-topurine, is employed during organ transplantation to suppress immunologic rejection.

HO H 5-Iodo-2'-deoxyuridine

5-Fluorouracil

HO OH 6-Azauridine

8-Azaguanine

NH 6-Mercaptopurine

NH 6-Mercaptopurine

6-Thioguanine

6-Thioguanine

Alloburinol

Alloburinol

Figure 33-12. Selected synthetic pyrimidine and purine analogs.

Nonhydrolyzable Nucleoside Triphosphate Analogs Serve as Research Tools

Synthetic nonhydrolyzable analogs of nucleoside triphosphates (Figure 33-13) 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.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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