Collect. Czech. Chem. Commun. 2001, 66, 1698-1706

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


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.