C-Glycosylphosphonyl Analogs of 5-Phosphorylribose 1-α-Diphosphate
| Autor: | Ronald W. McClard, John F. Witte |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
chemistry.chemical_classification
Stereochemistry Chemistry Metabolite Organic Chemistry medicine.disease_cause Biochemistry Yeast Glutamine chemistry.chemical_compound Drug Discovery Argument (complex analysis) medicine Orotate phosphoribosyltransferase Epimer Nucleotide Molecular Biology Escherichia coli |
| Zdroj: | Bioorganic Chemistry. 24:29-38 |
| ISSN: | 0045-2068 |
| DOI: | 10.1006/bioo.1996.0004 |
| Popis: | d - ribo -2,5-anhydro-1,3-dideoxy-1-(((dihydroxyphosphinyl)oxy)hydroxyphosphinyl)-6-phosphorylhexitol, compound 4, along with 25% of its d -arabino epimer, was synthesized in 10 steps from 2-deoxyribonolactone. Compound 4 represents the 2-deoxy analog of the central metabolite 5-phosphorylribose 1-α-diphosphate (PRPP). The analog is a competitive inhibitor of yeast orotate phosphoribosyltransferase (PRTase) with K i / K m (PRPP) = 24 and is thus comparable to other C -glycosylphosphonyl PRPP analogs reported previously (R. W. McClard, and J. F. Witte (1990) Bioorg. Chem. 18, 165–178). The analog is an even better inhibitor of both human hypoxanthine-guanine PRTase and glutamine:amido PRTase from Escherichia coli with K i / K m (PRPP) values of 16 and 3, respectively. These results support the argument that the cis-diol grouping of nucleotides (or PRPP) plays a very minor role in binding of these substrates to PRTases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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