PHOSPHONATE ANALOGS OF CARBOCYCLIC PHOSPHORIBOSYLAMINE AND CARBOCYCLIC GLYCINAMIDE RIBONUCLEOTIDE

Analogs of intermediates in the de novo purine nucleotide biosynthetic pathway were synthesized to study the binding requirements of the cor responding enzymes. Because of the instability of the natural stubstra tes, such as phosphoribosylamine, the use of the structurally stable p hosphonate moiety and the carbocyclic ribose yields ideal analogs for these studies. In addition, these analogs can act as potential inhibit ors of the de novo pathway leading to the design of anticancer agents. Enzyme studies with GAR synthetase and GAR transformylase reveal that the title compounds can act as substrates or inhibitors of the de nov o enzymes.