The antibiotic ganciclovir is a nucleotide analogon in use with immune supressed patients for infections with herpes simplex and cytomegalo virus. Also it was used in experimental genetic therapy with herpes thymidine kinase with maligne conditions. It's antiviral action is restricted to infected cells, because only virally coded kinases are able to phosphorylate it to the monophosphate. Further phosphorylation to the triphosphate is effected by cellular kinases. The resulting 5'-triphosphate can be incorporated into DNA, as the equivalent to the 3'-OH group of nucleosides exists. Chain elongation however is interrupted one base after the incorporation of ganciclovir by all polamerases investigated so far.
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| Deoxyguanosin dG |
Ganciclovir lG linear decarbo-C2' guanosine |
The molecular reason for the ceasing of chain elongation became clear when a systhetic DNA-decamer containing ganciclovir was structurally investigated by NMR spectroscopy.
Details of the structure may be viewed after a mouse click here.