Nucleotide analogs in medicine

See also Biosynthesis of Thymine Deoxyribonucleotides, Deoxyuridine Nucleotide Metabolism, Ribonucleotide Reductase and Deoxyribonucleotide Biosynthesis, Regulation of Ribonucleotide Reductase, Drug Design, Nucleotide Analogs in Medicine... 

Methylene THF, Nucleotide Analogs in Medicine, Gene Amplification... 

See also Nucleotide Analogs in Medicine, Nucleotide Salvage Synthesis, Salvage Routes to Deoxyribonucleotide Synthesis... 

Another group of inhibitors prevents nucleotide biosynthesis indirectly by depleting the level of intracellular tetrahydrofolate derivatives. Sulfonamides are structural analogs of p-aminobenzoic acid (fig. 23.19), and they competitively inhibit the bacterial biosynthesis of folic acid at a step in which p-aminobenzoic acid is incorporated into folic acid. Sulfonamides are widely used in medicine because they inhibit growth of many bacteria. When cultures of susceptible bacteria are treated with sulfonamides, they accumulate 4-carboxamide-5-aminoimidazole in the medium, because of a lack of 10-formyltetrahydrofolate for the penultimate step in the pathway to IMP (see fig. 23.10). Methotrexate, and a number of related compounds inhibit the reduction of dihydrofolate to tetrahydrofolate, a reaction catalyzed by dihydrofolate reductase. These inhibitors are structural analogs of folic acid (see fig. 23.19) and bind at the catalytic site of dihydrofolate reductase, an enzyme catalyzing one of the steps in the cycle of reactions involved in thymidylate synthesis (see fig. 23.16). These inhibitors therefore prevent synthesis of thymidylate in replicating... 

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