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Chemical Compound Review:

HPMPApp [[[(2S)-1-(6-aminopurin-9- yl)-3-hydroxy...

Synonyms: AC1LA2FU

Merta, A. et al., Chavalitshewinkoon-Petmitr, P. et al., Birkus, G. et al., Cerný, J. et al., Holý, A. et al.

Chavalitshewinkoon-Petmitr, Chawprom, Naesens, Balzarini, Wilairat,

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Disease relevance of HPMPApp

Thus, the inhibitory potency of HPMPApp and PMEApp toward HSV-1 encoded ribonucleotide reductase might be connected with the anti-HSV activity of HPMPA and PMEA [1].
These observations indicate that interaction of HPMPApp with pol alpha, delta and epsilon may contribute to its cellular toxicity and explain its antiviral activity against polyomavirus [2].

High impact information on HPMPApp

The enzyme isolated from a PMEA-resistant HSV-1 mutant proved less sensitive to PMEApp, hydroxyurea and HPMPApp [3].
When dATP was omitted from the reaction mixture, the addition of HPMPApp stimulated DNA synthesis by HSV-1 DNA polymerase indicating that HPMPApp is an alternative substrate for in vitro DNA synthesis catalyzed by this enzyme [4].
In addition, the DNA polymerase of parasite mitochondria was shown to be resistant (IC(50)>1 mM) to the nucleotide analogue (S)-1-[3-hydroxy-2-phosphonylmethoxypropyl]adenine diphosphate (HPMPApp) [5].

References

Phosphonylmethyl ethers of acyclic nucleoside analogues: inhibitors of HSV-1 induced ribonucleotide reductase. Cerný, J., Votruba, I., Vonka, V., Rosenberg, I., Otmar, M., Holý, A. Antiviral Res. (1990) [Pubmed]
The substrate activity of (S)-9-[3-hydroxy-(2-phosphonomethoxy)propyl]adenine diphosphate toward DNA polymerases alpha, delta and epsilon. Birkus, G., Rejman, D., Otmar, M., Votruba, I., Rosenberg, I., Holy, A. Antivir. Chem. Chemother. (2004) [Pubmed]
Acyclic nucleotide analogues: synthesis, antiviral activity and inhibitory effects on some cellular and virus-encoded enzymes in vitro. Holý, A., Votruba, I., Merta, A., Cerný, J., Veselý, J., Vlach, J., Sedivá, K., Rosenberg, I., Otmar, M., Hrebabecký, H. Antiviral Res. (1990) [Pubmed]
Inhibition of herpes simplex virus DNA polymerase by diphosphates of acyclic phosphonylmethoxyalkyl nucleotide analogues. Merta, A., Votruba, I., Rosenberg, I., Otmar, M., Hrebabecký, H., Bernaerts, R., Holý, A. Antiviral Res. (1990) [Pubmed]
Partial purification and characterization of mitochondrial DNA polymerase from Plasmodium falciparum. Chavalitshewinkoon-Petmitr, P., Chawprom, S., Naesens, L., Balzarini, J., Wilairat, P. Parasitol. Int. (2000) [Pubmed]

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