| An efficient biodelivery system for antisense polyamide nucleic acid (PNA). | |
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MedLine Citation:
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PMID: 18707540 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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With the aim of developing a general and straightforward procedure for the intracellular delivery of naked peptide nucleic acids (PNAs), we designed an intracellularly biodegradable triphenylphosphonium (TPP) cation based transporter system. In this system, TPP is linked, via a biolabile disulfide bridge, to an activated mercaptoethoxycarbonyl moiety, allowing its direct coupling to the N-terminal extremity of a free PNA through a carbamate bond. We found that such TPP-PNA-carbamate conjugates were highly stable in a cell culture medium containing fetal calf serum. In a glutathione-containing medium mimicking the cytosol, the conjugates were rapidly degraded into an unstable intermediate, which spontaneously decomposed, releasing the free PNA. Using a fluorescence-labeled PNA-TPP conjugate, we demonstrated that conjugates were taken up by cells. Efficient cellular uptake and release of the PNA into the cytosol was further confirmed by the anti-HIV activity measured for the TPP-conjugate of a 16-mer PNA targeting the TAR region of the HIV-1 genome. This conjugate exhibited an IC(50) value of 1 microM, while the free 16-mer PNA did not inhibit replication of HIV in the same cellular test. |
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Authors:
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Mohamed Mehiri; Gregory Upert; Snehlata Tripathi; Audrey Di Giorgio; Roger Condom; Virendra N Pandey; Nadia Patino |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Oligonucleotides Volume: 18 ISSN: 1557-8526 ISO Abbreviation: Oligonucleotides Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-09-15 Completed Date: 2009-04-13 Revised Date: 2011-06-06 |
Medline Journal Info:
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Nlm Unique ID: 101188415 Medline TA: Oligonucleotides Country: United States |
Other Details:
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Languages: eng Pagination: 245-56 Citation Subset: IM |
Affiliation:
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Laboratoire de Chimie des Molécules Bioactives et des Arômes, Université de Nice-Sophia Antipolis-CNRS, Institut de Chimie de Nice, Nice, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anti-HIV Agents
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metabolism,
pharmacology Antisense Elements (Genetics)* Cell Line Culture Media Drug Delivery Systems* HIV Long Terminal Repeat / drug effects HIV-1 / drug effects, genetics, physiology Humans Nylons / chemistry, metabolism* Peptide Nucleic Acids / chemical synthesis, metabolism*, pharmacology Virus Replication / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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AI42520/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-HIV Agents; 0/Antisense Elements (Genetics); 0/Culture Media; 0/Nylons; 0/Peptide Nucleic Acids |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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