Phosphorylation of carbovir enantiomers by cellular enzymes determines the stereoselectivity of antiviral activity
| Autor: | W H, Miller, S M, Daluge, E P, Garvey, S, Hopkins, J E, Reardon, F L, Boyd, R L, Miller |
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| Rok vydání: | 1992 |
| Předmět: |
Models
Molecular Molecular Structure Phosphotransferases Pyruvate Kinase Molecular Conformation Deoxyguanine Nucleotides HIV Stereoisomerism Templates Genetic Antiviral Agents Dideoxynucleosides Phosphoglycerate Kinase Reverse Transcriptase Inhibitors Phosphoenolpyruvate Carboxykinase (GTP) Phosphorylation Nucleoside-Phosphate Kinase Creatine Kinase Guanylate Kinases |
| Zdroj: | The Journal of biological chemistry. 267(29) |
| ISSN: | 0021-9258 |
| Popis: | Two enantiomers of carbovir, a carbocyclic analog of 2',3'-dideoxyguanosine, were compared with respect to their phosphorylation and the phosphorylation of their nucleotides by mammalian enzymes. 5'-Nucleotidase catalyzed the phosphorylation of (-)-carbovir, which is active against HIV (human immunodeficiency virus), but did not phosphorylate (+)-carbovir. (-)-Carbovir monophosphate was 7,000 times more efficient as a substrate for GMP kinase than was (+)-carbovir monophosphate. Pyruvate kinase, phosphoglycerate kinase, and creatine kinase phosphorylated both enantiomers of carbovir diphosphate at similar rates. Nucleoside-diphosphate kinase preferentially phosphorylated the (-)-enantiomer. Both enantiomers of carbovir triphosphate were substrates and alternative substrate inhibitors of HIV reverse transcriptase. Thus, the contrasting HIV-inhibitory activities of carbovir enantiomers were due to differential phosphorylation by cellular enzymes and not due to enantioselectivity of HIV reverse transcriptase. |
| Databáze: | OpenAIRE |
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