Why is the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine in its diphosphorylated form (PMEApp(4-)) initially a better substrate for polymerases than (2 '-deoxy)adenosine 5 '-triphosphate (dATP(4-)/ATP(4-))? Considerations on the mechanism of nucleic acid polymerases

Authors
Sigel, H Song, B Blindauer, CA Kapinos, LE Gregan, F Pronayova, N
Citation
H. Sigel et al., Why is the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine in its diphosphorylated form (PMEApp(4-)) initially a better substrate for polymerases than (2 '-deoxy)adenosine 5 '-triphosphate (dATP(4-)/ATP(4-))? Considerations on the mechanism of nucleic acid polymerases, CHEM COMMUN, (8), 1999, pp. 743-744
Citations number
20
Categorie Soggetti
Chemistry
Journal title
CHEMICAL COMMUNICATIONS
ISSN journal
13597345 → ACNP
Issue
8
Year of publication
1999
Pages
743 - 744
Database
ISI
SICI code
1359-7345(19990421):8<743:WITANA>2.0.ZU;2-6
Abstract
The observation that the antivirally active PMEA in its diphosphorylated fo rm (PMEApp(4-)) is initially a better substrate for polymerases than dATP(4 -) (ATP(4-)) can be rationalized by (i) the increased basicity of the phosp honyl group (compared to a phosphoryl group) and (ii) the participation of the ether O atom of PMEApp(4-) in metal ion binding; both effects together favor M2+ binding at the a group and thus its nucleophilic attack.