Chapter 23: PROBLEM 23.65 (page 1257)

Question. Retroviruses like HIV, the pathogen responsible for AIDS, incorporate an RNA template that is copied into DNA during infection. The reverse transcriptaseenzyme 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-2’,3’-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.
Draw the structures of AZT and natural deoxythymidine.
Draw the structure of AZT 5’-triphosphate, the derivative that inhibits reverse transcriptase.

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Retrovirus

A retrovirus is a biological term. It is a virus that uses RNA and has DNA intermediate in its life cycle.These are protein enveloped and one of the retroviruses is HIV, known as Human Immunodeficiency Virus.

Structure of AZT and natural deoxythymidine

AZT is an analog of thymidine deoxynucleoside and functions by inhibiting the HIV reverse transcriptase. Due to this, the progression of AIDS slows down and the virus's life cycle halts down. AZT is selective for HIV reverse transcriptase and blocks the activity of certain human polymerase enzymes

Structure of natural deoxythymidine

Structure of AZT

Structure of AZT 5’-triphosphate

AZT triphosphate inhibits DNA polymerase but has more affinity for HIV reverse transcriptase. It also inhibits HIV replication without affecting other functions of uninfected cells.

Structure of AZT 5’-triphosphate