Phosphorylation of 3'-azido-2',3'-dideoxyuridine and preferential inhibition of human and simian immunodeficiency virus reverse transcriptases by its 5'-triphosphate.

摘要: Abstract 3'-Azido-2',3'-dideoxyuridine-5'-triphosphate was found to be a potent and highly selective inhibitor of human immunodeficiency virus type 1 simian reverse transcriptases. The affinity 3'-azido-2',3'-dideoxyuridine-5'-triphosphate for the transcriptases similar that observed 3'-azido-3'-deoxythymidine-5'-triphosphate. Both compounds were competitive inhibitors with respect normal substrate dTTP served at least 100 times better as substrates than did dTTP. In contrast, cellular DNA polymerase alpha showed an about 60-times-higher preference either inhibitor. phosphorylation thymidine in peripheral blood mononuclear cell extracts inhibited manner by both 3'-azido-2',3'-dideoxyuridine 3'-azido-3'-deoxythymidine, apparent inhibition constants 290 3.4 microM, respectively. Michaelis-Menten constant, Km, 7.0 microM. 3'-Azido-2',3'-dideoxyuridine 3'-azido-3'-deoxythymidine substrates, Km values 67 1.4 maximal rates 40 30%, respectively, rate thymidine. different affinities kinase these may explain difference effects on replication infected cells when equimolar concentrations two are compared.