Interaction of 9-(1,3-dihydroxy-2-propoxymethyl)guanine with cytosol and mitochondrial deoxyguanosine kinases: possible role in anti-cytomegalovirus activity.

Abstract

The acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) is a potent inhibitor of human cytomegalovirus in vitro and in vivo. In order to investigate the phosphorylation of DHPG to the monophosphate and identify the enzyme responsible, attempts were made to isolate DHPG kinase from calf thymus and from human cytomegalovirus-infected lung cells. From calf thymus, a mitochondrial deoxyguanosine kinase was partially purified which co-migrated with DHPG phosphorylating activity on DEAE-cellulose, and had the same mobility by electrophoresis. DHPG triphosphate and DHPG kinase were elevated in cytomegalovirus-infected cells, but not enough enzyme activity was recovered to identify the kinase. However, DHPG was found to inhibit a cytosol deoxyguanosine kinase induced in these infected cells. The role of mitochondrial and cytosol deoxyguanosine kinases is discussed relative to the anti-cytomegalovirus activity of DHPG.