Interpretation of the roles of adenylosuccinate lyase and of AMP deaminase in the anti-HIV activity of 2',3'-dideoxyadenosine and 2',3'-dideoxyinosine

Abstract

Some 2',3'-dideoxynucleotides, of importance in the enzymology of the anti-HIV compounds, ddA and ddI, have been synthesized and purified by ion-exchange chromatography. 2',3'-Dideoxyadenylosuccinate, an intermediate in the pathway of ddI to ddATP, is converted to ddAMP by AMPS lyase at 1.85% of the efficiency of the natural substrate, adenylosuccinate. Interestingly, ddAMP and other 2',3'-dideoxygenated nucleotides are not substrates for AMP deaminase, another relevant enzyme in the conversion of ddA to ddATP via ddI.