Collection of Czechoslovak Chemical Communications.
2001 ;
66 (11) :
1698-1706.
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.
