Chemo-enzymatic synthesis of a new type of enantiomerically pure carbocyclic nucleoside analogues with strong inhibitory effects on terminal deoxynucleotidyl transferase
| Autor: | Sabine Flatau, Fritz Theil, Sibylle Ballschuh, Martin von Janta-Lipinski, Eckart Matthes |
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| Rok vydání: | 1998 |
| Předmět: |
Adenosine
DNA polymerase Stereochemistry Clinical Biochemistry Pharmaceutical Science Burkholderia cepacia Biochemistry Kinetic resolution Structure-Activity Relationship chemistry.chemical_compound DNA Nucleotidylexotransferase Drug Discovery Escherichia coli Animals Humans Hydroxymethyl Enzyme Inhibitors Telomerase Molecular Biology DNA Polymerase beta chemistry.chemical_classification biology Organic Chemistry Stereoisomerism Lipase DNA Polymerase I HIV Reverse Transcriptase Reverse transcriptase Kinetics Enzyme Terminal deoxynucleotidyl transferase chemistry biology.protein Reverse Transcriptase Inhibitors Molecular Medicine Cattle Enantiomer DNA polymerase I |
| Zdroj: | Bioorganic & Medicinal Chemistry. 6:701-706 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/s0968-0896(98)00021-2 |
| Popis: | The synthesis of enantiomerically pure carbocyclic adenosine derivatives which have been prepared based on the kinetic resolution of a trans -2-(hydroxymethyl)cyclopentanol derivative is described. Their corresponding triphosphates were evaluated as inhibitors of DNA polymerase β, terminal deoxynucleotidyl transferase (TdT), telomerase, Escherichia coli DNA polymerase I and reverse transcriptase of human immunodeficiency virus. Surprisingly, the triphosphate of (1 S ,2 R )-1-(6-aminopurin-9-yl)-2-(hydroxymethyl)cyclopentane [(1 S ,2 R )- 6 ] and its enantiomer (1 R ,2 S )- 6 emerged as strong inhibitors of TdT ( K i =0.5 and 1.9 mM, K mapp dATP=40 mM), whereas the activities of all other enzymes tested proved to be unaffected. |
| Databáze: | OpenAIRE |
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