Inhibition of HIV-1 replication in cultured cells with phosphorylated dideoxyuridine derivatives encapsulated in immunoliposomes
| Autor: | Alain Pompon, Helen Loughrey, Olivier Zelphati, Jean-Louis Imbach, Gilles Gosselin, Annie-Françoise Maggio, Lee Leserman, Geneviève Degols, F. Puech |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
medicine.drug_class
Uracil Nucleotides T cell Biology Monoclonal antibody Virus Replication Antiviral Agents Cell Line Drug Stability Virology medicine Humans Phosphorylation Pharmacology Liposome Dideoxynucleosides Kinase In vitro medicine.anatomical_structure Biochemistry Cell culture Liposomes HIV-1 Uridine Monophosphate Nucleoside Dideoxynucleotides |
| Zdroj: | Antiviral research. 21(3) |
| ISSN: | 0166-3542 |
| Popis: | Among the 2′,3′-dideoxynucleoside 5′-triphosphates containing a physiological base, 2′,3′-dideoxyuridine 5′-triphosphate (ddUTP) has been reported to be among the most powerful inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (RT) in cell-free systems. However, in contrast to other dideoxynucleosides, 2′,3′-dideoxyuridine (ddU) is inactive in treatment of HIV-infected cells in culture, since it is a poor substrate for cellular nucleoside kinases. This problem cannot be overcome by the use of phosphorylated ddU because such compounds are unable to cross cell membranes. To promote entry and thus bypass the limiting steps of intracellular phosphorylation, we have encapsulated mono- and tri-phosphorylated ddU in liposomes coupled to monoclonal antibodies (immunoliposomes). We investigated antiviral effects in two human T cell lines (MT-4, CEM). We observed that ddU nucleotides remain phosphorylated for several weeks after encapsulation in immunoliposomes, and potent antiviral activity is obtained when these drugs are delivered into infected cells by cell-specific antibodies (ED50 ⩽1 μM on CEM). In contrast, no inhibition was observed with non-targeted liposomes containing phosphorylated ddU, or with empty liposomes, whether targeted or not. |
| Databáze: | OpenAIRE |
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