Interpretation of the roles of adenylosuccinate lyase and of AMP deaminase in the anti-HIV activity of 2',3'-dideoxyadenosine and 2',3'-dideoxyinosine.
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.
Nair
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Department of Chemistry, University of Iowa, Iowa City 52242.
Sells
T B
TB
D000659:AMP Deaminase / Q000378:metabolism*; D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism; D000264:Adenylosuccinate Lyase / Q000378:metabolism*; D003838:Deoxyadenine Nucleotides / Q000096:biosynthesis / Q000378:metabolism; D016049:Didanosine / Q000378:metabolism* / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000378:metabolism* / Q000494:pharmacology; D054306:Dideoxynucleotides; D006678:HIV / Q000187:drug effects*; D013386:Succinates / Q000378:metabolism
D003838:Deoxyadenine Nucleotides; D054306:Dideoxynucleotides; D013386:Succinates; C073281:2',3'-dideoxyadenylosuccinate; C037773:2',3'-dideoxyadenosine triphosphate; C010110:2',3'-dideoxyadenosine 5'-phosphate; D016048:Dideoxyadenosine; D000659:AMP Deaminase; D000264:Adenylosuccinate Lyase; D016049:Didanosine; D000241:Adenosine