RT Journal Article
SR Electronic
T1 Metabolism and Mode of Inhibition of Varicella-Zoster Virus by<span class="sc">l</span>-β-5-Bromovinyl-(2-hydroxymethyl)-(1,3-dioxolanyl)uracil Is Dependent on Viral Thymidine Kinase
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1109
OP 1114
DO 10.1124/mol.58.5.1109
VO 58
IS 5
A1 Ling Li
A1 Ginger E. Dutschman
A1 Elizabeth A. Gullen
A1 Eisaku Tsujii
A1 Susan P. Grill
A1 Yongseok Choi
A1 Chung K. Chu
A1 Yung-chi Cheng
YR 2000
UL http://molpharm.aspetjournals.org/content/58/5/1109.abstract
AB A nonnaturally occurring l-configuration nucleoside analog,l-β-5-bromovinyl-(2-hydroxymethyl)-1,3-(dioxolanyl)uracil (l-BVOddU) selectively inhibited varicella-zoster virus growth in human embryonic lung (HEL) 299 cell culture with an EC50 of 0.055 μM, whereas no inhibition of CEM and HEL 299 cell growth or mitochondrial DNA synthesis was observed at concentrations up to 200 μM. l-BVOddU was phosphorylated by viral thymidine kinase but not by human cytosolic thymidine kinase, and the antiviral activity of this compound is dependent on the viral thymidine kinase. Unlike other d-configuration bromovinyl deoxyuridine analogs, such as E-5-(2-bromovinyl)-2′-deoxyuridine and 1-β-arabinofuranosyl-E-5-(2-bromovinyl)uracil, this compound was metabolized only to its monophosphate metabolite. The di- or triphosphate metabolites were not detected. This suggested that the inhibitory mechanism may be unique and different from other anti-herpesvirus nucleoside analogs.