Monophosphates and cyclic phosphates of some antiviral acyclonucleosides: synthesis, conformation and substrate/inhibitor properties in some enzyme systems.

Chemical and enzymatic procedures are described for the synthesis of the monophosphates and cyclic phosphates of the antiviral acyclonucleoside 9-(1,3-dihydroxy-2-propoxymethyl)-guanine (DHPG), its 3-hydroxymethyl-4-hydroxybutyl analogue, the (R)- and (S)-epimers of 9-(3,4-dihydroxybutyl)guanine, and 9-(2,3-dihydroxypropyl)guanine. The structures, and some conformational features, of all the foregoing, were determined by 1H and 31P NMR spectroscopy. Their substrate/inhibitor properties have been examined in several enzyme systems, including ribonucleases, snake venom phosphodiesterase, beef heart and higher plant cyclic nucleotide phosphodiesterases, nuclease P1, and 3'- and 5'-nucleotidases. The enzymatic results are considered in relation to the mechanism of the antiviral activity of the cyclic phosphate of DHPG.