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Title: Enzymatic Polymerization of Phosphonate Nucleosides
Authors: Renders, Marleen
Lievrouw, Roel
Krecmerova, Marcela
Holy, Antonin
Herdewijn, Piet # ×
Issue Date: Nov-2008
Publisher: Wiley-v c h verlag gmbh
Series Title: Chembiochem vol:9 issue:17 pages:2883-2888
Abstract: 5'-O-Phosphonomethyl-2'-deoxyadenosine (PMdA) proved to be a good substrate of the Therminator polymerose. In this article, we investigated whether the A, C, T and U analogues of this phosphonate nucleoside (PMdN) series can function as substrates of natural DNA polymerases. PMdT and PMdU could only be polymerized enzymatically to a limited extent, Nevertheless, PMdA and PMdC could be incorporated into a DNA duplex with complete chain elongation by all the DNA polymerases tested. A mixed sequence of four nucleotides containing modified C T and A residues could be obtained with the Vent(exo(-)) and Therminator polymerases. The kinetic values for the incorporation of PMdA by Vent(exo-) polymerase were determined; a reduced K-VI value was found for the incorporation of PMdA compared to the natural substrate. Future polymerase directed evolution studies will allow us to select an enzyme with a heightened capacity to process these modified DNA building blocks into modified strands.
ISSN: 1439-4227
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medicinal Chemistry (Rega Institute)
× corresponding author
# (joint) last author

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