9-BETA-D-ARABINOFURANOSYLADENINE 5'-MONOPHOSPHATE (ARAAMP) IS CONVERTED DIRECTLY TO ITS ANTIVIRALLY ACTIVE 5'-TRIPHOSPHATE FORM BY 5-PHOSPHORIBOSYL-1-PYROPHOSPHATE (PRPP) SYNTHETASE

The antiherpetic agent 9-β-D-arabinofuranosyladenine (araA) needs to be phosphorylated to its 5′-triphosphate to be effective as an inhibitor of herpes simplex virus replication. Adenosine kinase and deoxycytidine kinase are assumed to convert araA to its 5′-monophosphate. We now found that araAMP is converted to its 5′-triphosphate through a direct pyrophosphate transfer from 5-phosphoribosyl-1-pyrophosphate (PRPP) by PRPP synthetase. The efficiency of phosphorylation of araAMP to araATP is about 5% of that of AMP, as estimated from their Vmax/Km ratios for PRPP synthetase. AraATP is converted to araAMP by PRPP synthetase at a 4-fold higher Km but similar Vmax as ATP. © 1990 Academic Press, Inc.