Collect. Czech. Chem. Commun.
2001, 66, 1698-1706
https://doi.org/10.1135/cccc20011698
Interactions of 1-[(S)-3-Hydroxy-2-(phosphonomethoxy)propyl]cytosine (Cidofovir) Diphosphate with DNA Polymerases α, δ and ε*
Gabriel Birkuš, Ivan Votruba*, Miroslav Otmar and Antonín Holý
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic
Abstract
The inhibitory and/or substrate activity of 1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine [(S)-HPMPC, cidofovir, Vistide™] diphosphate towards eukaryotic DNA polymerases α, δ and ε* was examined. Cidofovir diphosphate is a weak competitive inhibitor of the above enzymes, approximately 3 to 7 times weaker than its adenine analogue (S)-HPMPApp. The enzymes also catalyze incorporation of (S)-HPMPC into DNA; after insertion of one (S)-HPMPC residue into DNA, another dNMP residue may incorporate. DNA polymerase δ and ε* can successively accommodate in the growing chain two (S)-HPMPC residues at the maximum, whereas pol α up to three residues.
Keywords: Nucleotides; Acyclic nucleoside phosphonates; Antivirals; Phosphates; (S)-HPMPC; Cidofovir; Vistide; (S)-HPMPA; Pol α; Pol δ; Pol ε.
References: 40 live references.
