Carbocyclic substrates for de novo purine biosynthesis. Enantiospecific synthesis and enantiospecificity of enzymatic utilization.
The carbocyclic analogues of phosphoribosylamine, glycinamide ribonucleotide, and formylglycinamide ribonucleotide have been prepared enantiospecifically from D-ribonic acid gamma-lactone. These carbocycles, which have the same absolute configuration as the natural D-ribose-derived intermediates of de novo purine biosynthesis, are utilized stoichiometrically by the initial enzymes of the pathway. A comparison of the enzymatic processing of the (-)-enantiomers with those of the racemates indicates that in some cases, the (+)-enantiomer acts to inhibit the enzymatic activity.
Caperelli
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CA
Division of Pharmacology & Medicinal Chemistry, College of Pharmacy, University of Cincinnati Medical Center, Ohio 45267-0004.
Liu
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D000217:Acyltransferases / Q000378:metabolism*; D019731:Carbon-Nitrogen Ligases; D019733:Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor; D019877:Hydroxymethyl and Formyl Transferases; D007536:Isomerism; D007700:Kinetics; D008025:Ligases / Q000378:metabolism*; D051026:Phosphoribosylglycinamide Formyltransferase; D011687:Purines / Q000378:metabolism*; D012265:Ribonucleotides / Q000138:chemical synthesis* / Q000378:metabolism; D012267:Ribosemonophosphates / Q000138:chemical synthesis* / Q000378:metabolism; D013379:Substrate Specificity
D011687:Purines; D012265:Ribonucleotides; D012267:Ribosemonophosphates; C008891:phosphoribosylamine; D019877:Hydroxymethyl and Formyl Transferases; D051026:Phosphoribosylglycinamide Formyltransferase; D000217:Acyltransferases; D008025:Ligases; D019731:Carbon-Nitrogen Ligases; C022387:phosphoribosylamine-glycine ligase; D019733:Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor; C022385:phosphoribosylformylglycinamidine synthetase