Phosphorylation of ganciclovir phosphonate by cellular GMP kinase determines the stereoselectivity of anti-human cytomegalovirus activity

A racemic mixture of ganciclovir phosphonate was resolved by stereoselectiv e phosphorylation using GMP kinase. The R-enantiomer of ganciclovir phospho nate was active against human cytomegalovirus but the S-enantiomer was less active. We show that enantiomeric selectivity of antiviral activity for ga nciclovir phosphonate was conferred by stereoselective phosphorylations by mammalian enzymes, not by stereoslective inhibition of DNA polymerase from human cytomegalovirus.