Nucleobase synthesis inhibition

Inhibition of nucleobase synthesis (2). Tetrahydrofolic acid (THF) is required for the synthesis of both purine bases and thymidine. Formation of THF from folic acid involves dihydrofolate reductase (p. 272). The folate analogues aminopterin and methotrexate (ame-thopterin) inhibit enzyme activity as false substrates. As cellular stores of THF are depleted, synthesis of DNA and RNA building blocks ceases. The effect of these antimetabolites can be reversed Ltillmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of iicense. 

Incorporation of false building blocks (3). Unnatural nucleobases (6-mercaptopurine 5-fluorouracil) or nucleosides with incorrect sugars (cytara-bine) act as antimetabolites. They inhibit DNA/RNA synthesis or lead to synthesis of missense nucleic acids. 

These points all refer to alteration of the inherent chemistry of the bases, which, although not emphasized in relation to platinum metal complexes and their antitumour activity, is a recognized lesion which may lead to cell kill through inhibition of DNA synthesis. Further features of metal—nucleobase chemistry are the dynamic features of... 

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