Title: Phosphodiester Substrates for Incorporation of Nucleotides in DNA Using HIV-1 Reverse Transcriptase
Authors: Giraut, Anne
Dyubankova, Natalia
Song, Xiao-Ping
Herdewijn, Piet # ×
Issue Date: Sep-2009
Publisher: Wiley-v c h verlag gmbh
Series Title: Chembiochem vol:10 issue:13 pages:2246-2252
Abstract: In previous research we demonstrated that some amino acid derivatives of deoxyadenosine 5'-O-monophosphate act as substrates for incorporation into DNA by HIV-1 reverse transcriptase while retaining the canonical base-pair selectivity for all natural bases. Thus, some amino acids mimic the pyrophosphate group in the polymerization process with this enzyme. Herein we extended this study to the evaluation of a range of potential new leaving groups with aromatic and aliphatic structures carrying one or two carboxylic acid functions. Out of this series, the isophthalic acid derivative of deoxyadenosine 5'-O-monophosphate gave single-nucleotide incorporation results similar to those obtained with the L-aspartic acid phosphoramidate of deoxyadenosine monophosphate. The glycolic acid analogue is a better substrate than the glycine congener, supporting the good leaving group properties of a phosphodiester linkage. These investigations provide new insight into the structural requirements for leaving groups that can mimic the pyrophosphate moiety of nucleoside triphosphates.
ISSN: 1439-4227
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medicinal Chemistry (Rega Institute)
Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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