Conversion of 2,6-diamino-9-(2-hydroxyethoxymethyl)purine to acyclovir as catalyzed by adenosine deaminase.

Adenosine deaminase (ADA) was partially purified from several sources using affinity chromatography. These enzymes have the capacity to catalyze the deamination of 2,6-diamino-9-(2-hydroxyethoxymethyl)purine (A134U) to form the antiviral agent acyclovir [9-(2-hydroxyethoxymethyl)guanine]. Their relative substrate efficiencies (Vmax/Km) with A134U (standardized to adenosine = 100) were: dog ADA, 0.092; human ADA, 0.015-0.029; rat ADA, 0.025; calf ADA, 0.016; and Escherichia coli ADA, 0.0003. In addition to having the lowest efficiency with A134U, the bacterial ADA was also distinguished by its lack of binding of the mammalian ADA inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine and by its weak binding to the 9-(p-aminobenzyl)adenine-agarose affinity column. Four minor metabolites of A134U and acyclovir have been reported to be produced in the rat. These compounds are oxidized on either the C-8 position of the ring or the terminal carbon of the side chain. Neither acyclovir nor any of these metabolites produced significant inhibition of calf intestine ADA. The oxidized metabolites containing an N-6 amino group were extremely slow substrates of this enzyme.