The diphosphate forms of the ANPs (i e CDVpp, PMEApp and PMPApp)

The diphosphate forms of the ANPs (i.e. CDVpp, PMEApp and PMPApp) interact as competitive inhibitors/alternative substrates with respect to the normal substrates (i.e. dCTP and dATP). Incorporation of one molecule of PMEApp or PMPApp

into the growing DNA strand results inevitably in DNA chain termination whereas CDVpp requires two consecutive Duvelisib cost incorporations to efficiently terminate DNA synthesis, as has been shown for HCMV (Xiong et al., 1996 and Xiong et al., 1997). The selective antiviral activity of ANPs results from the higher affinity of the ANPpp for viral DNA polymerases [that is herpesvirus and poxvirus DNA polymerases and HIV or HBV reverse transcriptases] than for cellular DNA polymerases α, δ, and ε. Fig. 1 illustrates the intracellular activation of CDV and its mode of action against viruses encoding for their own DNA polymerases. The mechanism of action of ANPs as antiviral agents has been extensively summarized in various reviews (De Clercq, 2003, Andrei and Snoeck, 2010, De Clercq, 2007, De Clercq, 2011 and De Clercq and Holy, 2005) and will not be further discussed here. Besides their well-recognized antiviral characteristics, CDV as well as some PME derivatives, Selleckchem Everolimus such as PMEA, PMEDAP

9-[(2-phosphonylmethoxy)ethyl]-2,6-diaminopurine and PMEG 9-[(2-phosphonylmethoxy)ethyl]guanine (Fig. 2), possess antiproliferative properties, although their mechanisms Oxalosuccinic acid of antitumor efficacy appear to be dissimilar considering that CDV is not an obligate chain terminator, in contrast to the PME derivatives, and that the effects of CDVpp on cellular DNA polymerization are weaker compared to the

diphosphate forms of the PME derivatives (Wolfgang et al., 2009). In this review, we focus on the antiproliferative activities of ANPs and we debate on their mode of action against viruses, such as polyomaviruses (PyVs) and papillomaviruses (PVs) that do not encode for their own DNA polymerases. Also, the potential use of ANPs for the treatment of non-viral induced tumors will be discussed. Until 2000, PVs and PyVs were grouped together in the family Papovaviridae (“pa–po–va” stands for papilloma–polyoma–vacuolizing agent SV40). Since then, the family Papovaviridae is obsolete and the Papillomaviridae and Polyomaviridae families were recognized by the International Committee on Taxonomy of Viruses (ICTV) (Johne et al., 2011 and de Villiers et al., 2004). Table 2 summarizes the main similarities and differences between PyVs and PVs. These two viral families have a non-enveloped icosahedral capsid (composed of 72 capsomers) surrounding a double-stranded circular DNA genome of ∼5 kbp in PyVs and of ∼8 kbp in PVs. Both viruses use overlapping genes and differential splicing to pack the maximum amount of genetic material in the minimum space.

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