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Issue 3, 2004
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Metal ion complexes of antivirally active nucleotide analogues. Conclusions regarding their biological action

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Abstract

Acyclic nucleoside phosphonates (ANPs), i.e., analogues of (2′-deoxy)nucleoside 5′-monophosphates, have been studied during the past 15 years for their potential as antiviral drugs. One of these compounds, 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA; Adefovir) was recently approved in the form of its bis(pivaloyloxymethyl)ester (Adefovir dipivoxil) for use in hepatitis B therapy, a disease evoked by a DNA virus. Diphosphorylated PMEA2−, i.e., PMEApp4−, is initially recognized by nucleic acid polymerases as an excellent substrate, but after insertion in the growing nucleic acid chain, this is terminated due to the lack of a 3′-hydroxy group. Based on the metal ion-binding properties of PMEApp4− it can be explained why the ether oxygen in the aliphatic chain, R–CH2–O–CH2–PO3pp4−, is compulsory for a useful biological activity. Consequently, this critical review presents an overview on the coordination chemistry of various ANPs and correlates this to their biological properties.

Graphical abstract: Metal ion complexes of antivirally active nucleotide analogues. Conclusions regarding their biological action

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Publication details

The article was received on 26 Aug 2003 and first published on 10 Feb 2004


Article type: Critical Review
DOI: 10.1039/B310349H
Chem. Soc. Rev., 2004,33, 191-200

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    Metal ion complexes of antivirally active nucleotide analogues. Conclusions regarding their biological action

    H. Sigel, Chem. Soc. Rev., 2004, 33, 191
    DOI: 10.1039/B310349H

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