Thymidine-5 -phosphate, structure

Acyclovir (ACV) is not a true nucleoside, because the guanine residue is attached to an open-chain structure, but it mimics deoxyribose well enough for the compound to be accepted as a substrate by a thymidine kinase specified by certain herpes-type viruses. The normal thymidine kinase in mammalian cells does not recognize ACV as a substrate, however, so only virus-infected cells convert ACV to its monophosphate. Once the first phosphate has been added, the second phosphate is added by cellular guanylate kinase several other cellular kinases can add the third phosphate. The triphosphate is a more potent inhibitor of the viral DNA polymerases than of cellular DNA polymerases and also inactivates the former but not the latter. The net result is that ACV has been an effective treatment of, and prophylaxis for, genital herpes. Also it can result in dramatic relief of pain associated with shingles caused by reactivation of latent varicella-zoster virus, and has been successful in many patients with herpes encephalitis. 

Bases from two different strands interact to form a double-helical structure. Guanine forms three hydrogen bonds with cytosine, whereas adenine forms two hydrogen bonds with thymidine. Stacking interactions between the planar bases also stabilize the DNA structure. Phosphates and sugars form the backbone of DNA. 

The structures of 1,3,2-dioxaphosphinanes of biochemical significance to have been solved by x-ray crystallography are numerous the phenyl ester of thymidine 3, 5 -cyclic phosphate is an example <75PNA(72)1335, 87JA4058>. In the 1,3,5-dioxaphosphinane series, conformational studies by NMR have been supported by x-ray crystal structures <87IZV418>. 

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