Nucleic Acid Structure and Function: Drugs Exam Questions And Complete Answers.
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Course
AZAT
Institution
AZAT
Anti-Viral Nucleoside Analogues (AZT) - correct answer --> Viral reverse transcriptase inhibitors
Nucleoside analogues--->
-Molecules that act like nucleosides in DNA synthesis. Include a range of antiviral products used to prevent viral repli...
-Molecules that act like nucleosides in DNA synthesis. Include a range of antiviral products used to
prevent viral replication in infected cells.
Anti-Viral Nucleoside Analog-->
1) Azidothymidine (AZT) Zidovudine-->
-It is a thymidine analog. AZT is identical to deoxythymidine in every way except at the 3' OH position. At
the 3' OH position of deoxythymidine we have 3'-OH group (which is important for building
phosphodiester bond).
-Whereas AZT has nitrogens at position 3' (since there are no -OHs, you are not able to produce a
phosphodiester bond and so if you incorporate AZT into the growing DNA strand (like HIV DNA) it won't
continue the process of polymerization. Synthesis stops because is no free 3'OH group to continue the
process of polymerization.
-AZT has greater affinity for reverse transcriptase than it does for DNA polymerase.
Summary:
AZT (utilized by viral reverse transcriptase) ---> Upon incorportation into dsDNA chain termination
occurs due to the lack of 'OH
, Zidovudine can-->
1) Prolong life in HIV+ individuals
2) Reduce mother to baby transmission by more than 20%
--> In order for Azidothymidine (AZT) to be incorporated into the DNA of HIV virus it needs to be
phosphorylated and converted into a nucleotide. This is accomplished by host cellular kinases.
--> AZT (pro-drug---> goes into our body and becomes phosphorylated so it can be incorporated into
growing DNA chain).
Anti-viral nucleoside analog: Didanosine (ddl) - correct answer --> Used for
treatment of HIV in combination with other anti-virals.
--> Deoxyadenosine analog (similar to deoxythymidine)
-Deoxyadenosine structure is similar to didanosine except there is no 3'-OH group in didanosine.
So when didanosine gets incorporated into a growing DNA chain, it is going to cause termination.
But because it is a nucleoside analog, it needs to be phosphorylated by host cellular kinases before it can
have its effect. (It will be phosphorylated so it can be used by reverse transcriptase and will halt reverse
transcriptase activity).
Summary of Didanosine mechanism of action--->
1) Utilized by viral reverse transcriptase --->
2) Upon incorporation into dsDNA chain termination occurs due to lack of 3'OH --->
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