Imporved biological activity of antisense oligonucleotides conjugated to a fusogenic peptide
| Autor: | Bernard Lebleu, Anne-Marie Aubertin, J P Bongartz, P G Milhaud |
|---|---|
| Přispěvatelé: | Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM) |
| Rok vydání: | 1994 |
| Předmět: |
Hemagglutinin Glycoproteins
Influenza Virus Peptide 01 natural sciences Influenza Virus Hemagglutinins Culture Media Serum-Free Lymphocytes Peptide sequence Cells Cultured chemistry.chemical_classification Drug Carriers 0303 health sciences Amino Acid Sequence Antiviral Agents/*pharmacology Bacterial Proteins/chemistry Base Sequence Cell Membrane/drug effects Cells Biological activity Transfection 3. Good health Cross-Linking Reagents Oligodeoxyribonucleotides Biochemistry Gene Products tat tat Gene Products Human Immunodeficiency Virus Human Immunodeficiency Virus Molecular Sequence Data Hemagglutinins Viral Gene delivery Biology Antiviral Agents tat HIV-1/*drug effects/growth & development Hemagglutinin Glycoproteins Viral/*chemistry Liposomes Lymphocytes/virology Molecular Sequence Data Oligodeoxyribonucleotides/chemistry Oligonucleotides 03 medical and health sciences Serum-Free Drug Carriers Fibroblasts/virology Gene Products Bacterial Proteins Genetics [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Amino Acid Sequence 030304 developmental biology Reporter gene Base Sequence 010405 organic chemistry Oligonucleotide Cell Membrane Fibroblasts Oligonucleotides Antisense Thionucleotides Cultured Cross-Linking Reagents Culture Media Molecular biology 0104 chemical sciences Antisense/chemistry/*pharmacology Peptides/chemical synthesis/*chemistry/pharmacology Streptavidin Thionucleotides/chemistry tat Gene Products chemistry Liposomes Phosphodiester bond HIV-1 Streptavidin Peptides |
| Zdroj: | Nucleic Acids Research Nucleic Acids Research, Oxford University Press, 1994, 22 (22), pp.4681--8. ⟨10.1093/nar/22.22.4681⟩ |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/22.22.4681 |
| Popis: | Recently several groups reported a dramatic improvement of reporter gene transfection efficiency using a fusogenic peptide, derived from the Influenza hemagglutinin envelop protein. This peptide changes conformation at acidic pH and destabilizes the endosomal membranes thus resulting in an increased cytoplasmic gene delivery. We describe the use of a similar fusogenic peptide in order to improve the antiviral potency of antisense oligodeoxynucleotides (anti TAT) and oligophosphorothioates (S-dC28) on de novo HIV infected CEM-SS lymphocytes in serum-free medium. We observed as 5 to 10 fold improvement of the anti HIV activities of the phosphodiester antisense oligonucleotides after chemical coupling to the peptide in a one to one ratio by a disulfide or thioether bond. No toxicities were observed at the effective doses (0.1-1 microM). No sequence specificity was obtained and the fusogenic peptide possessed some antiviral activities on its own (IC50: 6 microM). A S-dC28-peptide disulfide linked conjugate and a streptavidin-peptide-biotinylated S-dC28 adduct showed similar activities as the free S-dC28 oligonucleotide (IC50: 0.1-1 nM). As expected, all the compounds were less potent in the presence of serum but the relative contribution of peptide coupling was maintained. |
| Databáze: | OpenAIRE |
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