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. 1991 Oct;35(10):2121–2124. doi: 10.1128/aac.35.10.2121

Anabolic pathway of 6-methoxypurine arabinoside in cells infected with varicella-zoster virus.

P de Miranda 1, T C Burnette 1, K K Biron 1, R L Miller 1, D R Averett 1, T A Krenitsky 1
PMCID: PMC245337  PMID: 1662024

Abstract

6-Methoxypurine arabinoside (ara-M) exhibits potent activity against varicella-zoster virus (VZV) as a result of ara-M's anabolism to the triphosphate of adenine arabinoside (ara-ATP) in VZV-infected cells. The adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) enhanced the formation of ara-ATP by inhibiting ara-M demethoxylation. In contrast, deoxycoformycin and coformycin, inhibitors of both adenosine deaminase and AMP deaminase, blocked the formation of ara-ATP and reversed the anti-VZV activity of ara-M. These results indicate that after the initial phosphorylation of ara-M by the VZV-coded thymidine kinase, the monophosphate is demethoxylated by AMP deaminase to form ara-IMP, which is converted to ara-ATP by the sequential actions of the cellular adenylosuccinate synthetase, adenylosuccinate lyase, and nucleotide kinases.

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Selected References

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