Purine Analogs selective kinase

The characteristics of the metabolic changes imposed on the cell by HSV-1 versus HSV-2 appear to be different enough to affect the drug therapy used against these viruses. Specifically, the second step of BrVdUrd phosphorylation appears to be more selective than the first step and may help determine the effectiveness of the analog to inhibit virus replication. The apparent dependence of some pyrimidine derivatives on the virus-associated dThd-dTMP kinase for both phosphorylation steps may be a crucial difference between these compounds and the purine analog, acyclovir. 

The establishment by Littlefield (1964) of a selective system, analogous to that used in microbial genetics, for the detection of rare hybrids between cell lines carrying different drug-resistance markers, correlated with deficiencies in the enzymatic pathways required for phosphorylation of preformed thymidine and hypoxanthine. Cell lines characterized by deficiency of thymidine kinase or ino-sinic acid pyrophosphorylase are therefore unable to survive in the presence of aminopterin (an inhibitor of the de novo synthesis of purines and pyrimidines) even if the appropriate bases are supplied in the medium, while hybrid cells, restored to the full complement of enzymes, grow normaDy. 

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