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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.

  1. Draw the structures of AZT and natural deoxythymidine.
  2. Draw the structure of AZT 5’-triphosphate, the derivative that inhibits reverse transcriptase.

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01

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.

02

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

03

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

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Most popular questions from this chapter

The carbonyl group in D-galactose may be isomerized from C1 to C2 by brief treatment with dilute base (by enediol rearrangement, Section 23-7). The product is the C4 epimer of fructose. Draw the furanose structure of the product.

The relative configurations of the stereoisomers of tartaric acid were established by the following synthesis:

(1) D-(+)-glyceraldehydediastereomers A and B (separated)

(2) Hydrolysis of A and B using aqueous Ba(OH)2 gave C and D, respectively.

(3) HNO3 oxidation of C and D gave (-)-tartaric acid and meso-tartaric acid, respectively.

(a) You know the absolute configuration of D-(+)-glyceraldehyde, Use Fischer projections to show the absolute configurations of products A, B, C, and D.

(b) Show the absolute configurations of the three stereoisomers of tartaric acid: (+)-tartaric acid, (-)-tartaric acid, and meso-tartaric acid.

Predict the products formed when the following sugars react with excess acetic anhydride and pyridine.

  1. α-D-glucopyranose
  2. β-D-ribofuranose

After a series of Kiliani–Fischer syntheses on (+)-glyceraldehyde, an unknown sugar is isolated from the reaction mixture. The following experimental information is obtained:

(1) Molecular formula C6H12O6

(2) Undergoes mutarotation.

(3) Reacts with bromine water to give an aldonic acid.

(4) Reacts with HNO3 to give an optically active aldaric acid.

(5) Ruff degradation followed by HNO3 oxidation gives an optically inactive aldaric acid. (6) Two Ruff degradations followed by HNO3 oxidation give meso-tartaric acid.

(7) When the original sugar is treated with CH3I and Ag2O, a pentamethyl derivative is formed. Hydrolysis gives a tetramethyl derivative with a free hydroxy group on C5.

(a) Draw a Fischer projection for the open-chain form of this unknown sugar. Use Figure 23-3 to name the sugar.

(b) Draw the most stable conform

All of the rings of the four heterocyclic bases are aromatic. This is more apparent when the polar resonance forms of the amide groups are drawn, as is done for thymine at left. Redraw the hydrogen-bonded guanine-cytosine and adenine-thymine pairs shown in figure 23-24, using the polar resonance forms of the amides. Show how these forms help to explain why the hydrogen bonds involved in these pairings are particularly strong. Remember that a hydrogen bond arises between an electron-deficient hydrogen atom and electron-rich pair of nonbonding electrons.

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