Looking for new pyrimidine acyclic nucleotide analogues designed for phosphorylation by human UMP-CMP kinase. 
Human UMP-CMP kinase is involved in the phosphorylation of nucleic acid precursors and also in the activation of antiviral analogues including cidofovir, an acyclic phosphonate compound that mimicks dCMP and shows a broad antiviral spectrum.  The binding of ligands to the enzyme was here investigated using a fluorescent probe and a competitive titration assay.  At the acceptor site, the enzyme was found to accommodate any base, purine and pyrimidine, including thymidine.  A method for screening analogues based on their affinity for the UMP binding site was developed.  The affinities of uracil vinylphosphonate derivatives modified in the 5 position were found similar to (d)UMP and (d)CMP and improved when compared to cidofovir.