DNA Replication Inhibition by Nucleoside Analogs

DNA chain growth can be blocked by the incorporation of certain nucleoside analogs that have been modified on the sugar portion (Fig. 1). For example, removal of the hydroxyl group from the 3′-carbon of the deoxyribose ring as in 2′,3′-dideoxyinosine ([ddI] also known as didanosine), or conversion of the deoxyribose to another sugar, such as arabinose, prevents further chain elongation. By blocking DNA replication, these compounds slow the division of rapidly growing cells and viruses.
Cytosine arabinoside (cytarabine, or araC) has been used in anticancer chemotherapy, whereas adenine arabinoside (vidarabine, or araA) is an antiviral agent. Substitution on the sugar moiety, as seen in azidothymidine (AZT), also called zidovudine (ZDV), also terminates DNA chain elongation. [Note: These drugs are generally supplied as nucleosides, which are then converted to nucleotides by cellular kinases.]

Figure 1:  Examples of nucleoside analogs that lack a 3′-hydroxyl group. [Note: The ddI is converted to its active form (dideoxy ATP).]