Chapter 23, Problem 23.65SP

Retroviruses like HIV, the pathogen responsible for AIDS, incorporate an RNA template that is copied into DNA during infection. The reverse transcriptase enzyme that copies RNA into DNA is relatively nonselective and error-prone, leading to a high mutation rate. Its lack of selectivity is exploited by the anti-HIV drug AZT (3′ — azido – 23′ – dideoxythymidine), which becomes phosphorylated and is incorporated by reverse transcriptase into DNA where it acts as a chain terminator. Mammalian DNA polymerases are more selective, having a low affinity for AZT, so its toxicity is relatively low.

1. a. Draw the structures of AZT and natural deoxythymidine.
2. b. Draw the structure of AZT 5′ – triphosphate, the derivative that inhibits reverse transcriptase.