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Kaplan Qbank USMLE



Author8 Posts
  #1

Hi all,

Can you please explain me the mechanism of acyclovir..How does it cause chain termination when incorporated into the viral DNA after being phosphorylated????

  #2

It an anitmetabolite. Also called acylcoguanosine. Mimics a guanine resiue but does not allow the polermerase to continue past it in replication. Hope that helps.

  #3

Thanks a lot ankylostoma.One more query...I am not sure about why ganciclovir is effective against CMV ,while acyclovir is not...Book says there is some change in DNA polymerase which does not cause chain termination

  #4

this is a easyone , acyclovir is activated by a viral thymidine kinase, this kinase isnt present in CMV, instead it has a phophotransferase. Gancyclovir is activated by the phophotransferase or thymidine kinase. This is why its used as a treatment in CMV(phosphotransferase) and can be used as a backup in HSV, (thymidine kinase)

Remember that both drugs require activation via a thymidine kinase (acyclovir, gangcyclovir) or phospotransferase (Gancyclovir). The thymidine kinase require to activate acyclovir is not present in CMV and thus acyclovir doesnot have any efficacy. Finally because ganciclovir can be activated by either enzyme, it is has efficacy against HSV and CMV.

Good luck

  #5

Thanks bro....However,why does chain termination doesn't occur in ganciclovir while it occurs in Acyclovir..Is ganciclovir is an analog of guanosine like acyclovir..?

  #6

Looks like you got me there, I will look it up but I cant remember

  #7

ah found it , while acyclovir causes chain termincation because it lacks the 3' hydroxyl group required for the creation of the phosphodiester bond, gancyclovir has this hydroxy and thus can be incorporated into the dna. It seems a little wierd but there isnt a better explanation in my kaplan notes.

  #8

Thanks againnod

One more..But not in this forum.IN Bio-chemistry forumsmiling face







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