Stability of Stereoregular Oligo(nucleoside Phosphorothioate)s in Human Plasma: Diastereoselectivity of Plasma 3‵-Exonuclease
| Autor: | Marzena Wojcik, Wojciech J. Stec, Bolesław Karwowski, Anna Kobylańska, Beata Rȩbowska, Maria Koziołkiewicz, Piotr Guga |
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| Rok vydání: | 1997 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Exonuclease biology Stereochemistry Diastereomer Substrate (chemistry) Stereoisomerism Thionucleotides Enzyme assay Nucleobase Exodeoxyribonucleases Enzyme Drug Stability chemistry Genetics biology.protein Humans Nucleic Acid Conformation Electrophoresis Polyacrylamide Gel Nucleoside |
| Zdroj: | Antisense and Nucleic Acid Drug Development. 7:43-48 |
| ISSN: | 1087-2906 |
| DOI: | 10.1089/oli.1.1997.7.43 |
| Popis: | The stability of stereoregular oligo(nucleoside phosphorothioate)s (PS-oligos) in human plasma has been studied. 3'-Exonuclease present in human plasma appeared to be RP specific, that is, it cleaves internucleotide phosphorothioate linkages of [RP]-configuration and not those of [SP]-configuration. Therefore, PS-oligos containing all phosphorothioate internucleotide linkages of [RP]-configuration [RP-PS-oligos]) are more effectively degraded by the enzyme than PS-oligos prepared via nonstereo-controlled methods (so-called random mixture of diastereomers [Mix-PS-oligos]), whereas oligo(nucleoside phosphorothioate)s of [S(P)]-configuration remain intact. The enzyme activity depends on the sequence of nucleobases. The presence of deoxycytidine units (three or more residues) at the 3'-end of PS-oligo substrate significantly inhibits the enzyme activity. |
| Databáze: | OpenAIRE |
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