Metal ion complexes of antivirally active nucleotide analogues. Conclusions regarding their biological action |
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Authors: | Sigel Helmut |
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Institution: | Department of Chemistry, Inorganic Chemistry, University of Basel, Spitalstrasse 51, CH-4056 Basel, Switzerland. Helmut.Sigel@unibas.ch |
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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 PMEA(2-), i.e., PMEApp(4-), 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 PMEApp(4-) it can be explained why the ether oxygen in the aliphatic chain, R-CH(2)-O-CH(2)-PO(3)pp(4-), 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. |
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