Skip Navigation

This Article
Right arrow Print PDF (2224K)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (116)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Bongartz, J.-P.
Right arrow Articles by Lebleu, B.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Bongartz, J.-P.
Right arrow Articles by Lebleu, B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 1994, Vol. 22, No. 22 4681-4688
© 1994

CHEMISTRY

Imporved biological activity of antisense oligonucleotides conjugated to a fusogenic peptide

Jean-Pierre Bongartz, Anne-Marie Aubertain1, Pierre G. Milhaud and Bernard Lebleu*

Institut de Génétique Moléculaire de Montpellier–UMR CNRS 9942 1919 route de Mende, 34033 Montpellier 1 U 74 INSERM, Faulté de Médecine, Laboratoire de Virologie, Université Louis Pasteur 3rue de Koeberlé, 67000 Strasbourg, France

*To whom correspondence should be addressed

Received July 8, 1994. Revised October 6, 1994. Accepted October 14, 1994.

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 a 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 µM). No sequence specificity was obtained and the fusogenic peptide possessed some antiviral activities on its own (IC50: 6 µM). A S-dC28 – peptide disulfide linked conjugate and a streptavidin - peptidebiotinylated 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.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
P. C. Patel, D. A. Giljohann, D. S. Seferos, and C. A. Mirkin
Nanomaterials in Medicine Special Feature Sackler Colloquium: Peptide antisense nanoparticles
PNAS, November 11, 2008; 105(45): 17222 - 17226.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
V. Marchan, S. Ortega, D. Pulido, E. Pedroso, and A. Grandas
Diels-Alder cycloadditions in water for the straightforward preparation of peptide-oligonucleotide conjugates
Nucleic Acids Res., February 14, 2006; 34(3): e24 - e24.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J. J. Turner, A. A. Arzumanov, and M. J. Gait
Synthesis, cellular uptake and HIV-1 Tat-dependent trans-activation inhibition activity of oligonucleotide analogues disulphide-conjugated to cell-penetrating peptides
Nucleic Acids Res., January 7, 2005; 33(1): 27 - 42.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
F. A. Rogers, M. Manoharan, P. Rabinovitch, D. C. Ward, and P. M. Glazer
Peptide conjugates for chromosomal gene targeting by triplex-forming oligonucleotides
Nucleic Acids Res., December 15, 2004; 32(22): 6595 - 6604.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
Y.-L. Tseng, J.-J. Liu, and R.-L. Hong
Translocation of Liposomes into Cancer Cells by Cell-Penetrating Peptides Penetratin and Tat: A Kinetic and Efficacy Study
Mol. Pharmacol., October 1, 2002; 62(4): 864 - 872.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
N. Mignet, A. Brun, C. Degert, B. Delord, D. Roux, C. Helene, R. Laversanne, and J.-C. Francois
The spherulitesTM: a promising carrier for oligonucleotide delivery
Nucleic Acids Res., August 15, 2000; 28(16): 3134 - 3142.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
C. Pichon, M. B. Roufai, M. Monsigny, and P. Midoux
Histidylated oligolysines increase the transmembrane passage and the biological activity of antisense oligonucleotides
Nucleic Acids Res., January 15, 2000; 28(2): 504 - 512.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
V. Prasad, S. Hashim, A. Mukhopadhyay, S. K. Basu, and R. P. Roy
Oligonucleotides Tethered to a Short Polyguanylic Acid Stretch Are Targeted to Macrophages: Enhanced Antiviral Activity of a Vesicular Stomatitis Virus-Specific Antisense Oligonucleotide
Antimicrob. Agents Chemother., November 1, 1999; 43(11): 2689 - 2696.
[Abstract] [Full Text]

Home page
 BloodHome page
A. M. Gewirtz, D. L. Sokol, and M. Z. Ratajczak
Nucleic Acid Therapeutics: State of the Art and Future Prospects
Blood, August 1, 1998; 92(3): 712 - 736.
[Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Vives, P. Brodin, and B. Lebleu
A Truncated HIV-1 Tat Protein Basic Domain Rapidly Translocates through the Plasma Membrane and Accumulates in the Cell Nucleus
J. Biol. Chem., June 20, 1997; 272(25): 16010 - 16017.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.