Cell penetrating PNA constructs regulate galanin receptor levels and modify pain transmission in vivo

Pooga, Margus; Soomets, Ursel; Hällbrink, Mattias; Valkna, Andres; Saar, Külliki; Rezaei, Khadijeh; Kahl, Ulrika; Hao, Jing‐Xia; Xu, Xiao‐Jun; Wiesenfeld‐Hallin, Zsuzsanna; Hökfelt, Tomas; Bartfai, Tamás; Langel, Ülo

doi:10.1038/nbt0998-857

Cited by 562 publications

(334 citation statements)

References 28 publications

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“…29,30 These peptides may also be used as transport peptides to facilitate translocation of other molecules, such as peptide nucleic acid (PNA), across biological membranes. 31 In this study, we have used the cellpenetrating peptides, TP and its N-terminally truncated analogue transportan 10 (TP10), to increase the cellular uptake of oligonucleotide transcription factor decoy. TP is a 27 amino-acid-long peptide (galanin (1-12)-Lysmastoparan (1-14) amide).…”

Section: Introductionmentioning

confidence: 99%

Cellular delivery of a double-stranded oligonucleotide

et al. 2004

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The activation of nuclear factor kB (NFkB) is a key event in immune and inflammatory responses. In this study, a cellpenetrating transport peptide, transportan (TP) or its shorter analogue TP 10, was used to facilitate the cellular uptake of an NFkB decoy. Peptide nucleic acid (PNA) hexamer or nonamer was linked to the transport peptide by a disulfide bond. NFkB decoy oligonucleotide consisted of a doublestranded consensus sequence corresponding to the kB site localized in the IL-6 gene promoter, 5 0 -GGGACTTTCCC-3 0 , with a single-stranded protruding 3 0 -terminal sequence complementary to the PNA sequence was hybridized to the transport peptide-PNA construct. The ability of the transport peptide-PNA-NFkB decoy complex to block the effect of interleukin (IL)-1b-induced NFkB activation and IL-6 gene expression was analyzed by electrophoretic mobility shift assay and reverse transcriptase-polymerase chain reaction in rat Rinm5F insulinoma cells. Preincubation with transport peptide-PNA-NFkB decoy (1 mM, 1 h) blocked IL-1b-induced NFkB-binding activity and significantly reduced the IL-6 mRNA expression. The same concentration of NFkB decoy in the absence of transport peptide-PNA had no effect even after longer incubations. Our results showed that binding of the oligonucleotide NFkB decoy to the nonamer PNA sequence resulted in a stable complex that was efficiently translocated across the plasma membrane.

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Section: Introductionmentioning

confidence: 99%

Cellular delivery of a double-stranded oligonucleotide

et al. 2004

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“…Historically, two hypotheses were put forward to explain how these peptides could possibly deliver various kinds of molecules, and also much larger macromolecular structures, into the cell (for a review [16]). It was first proposed that CPPs, especially Tat and Antennapedia, but also others such as poly-Arg [10,26], Transportan [27], MPG [28] or Pep-1 [20], could pass through the plasma membrane via an energy-independent pathway. Some suggestions have been put forward to explain the translocation of these peptides, such as the formation of micromicelles at the membrane [5], or direct translocation through the lipid bilayer [29,30].…”

Section: Cpps and Cell Entrymentioning

confidence: 99%

Cell-penetrating and cell-targeting peptides in drug delivery

Vivès

Schmidt

Pèlegrin

2008

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

315

272

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During the last decade, the potential of peptides for drug delivery into cells has been highlighted by the discovery of several cell-penetrating peptides (CPPs). CPPs are very efficient in delivering various molecules into cells. However, except in some specific cases, their lack of cell specificity remains the major drawback for their clinical development. At the same time, various peptides with specific binding activity for a given cell line (cell-targeting peptides) have also been reported in the literature. One of the goals of the next years will be to optimize the tissue and cell delivery of therapeutic molecules by means of peptides which combine both targeting and internalization advantages. In this review, we describe the main strategies that are currently in use or likely to be employed in the near future to associate both targeting and delivery properties.

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“…Linkage of so-called cell-penetrating peptides (CPPs) 1 to other molecules mediates the non-invasive import of these cargo molecules into cells ex vivo as well as in whole animals (4,5). Cargos have been peptides (6,7), proteins as large as 120 kDa (5,8), oligonucleotides (9), plasmids (10), peptide nucleic acids (11), and even nanoparticles (12).…”

mentioning

confidence: 99%

A Stepwise Dissection of the Intracellular Fate of Cationic Cell-penetrating Peptides

Fischer

Köhler

Fotin‐Mleczek

et al. 2004

Journal of Biological Chemistry

270

289

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The role of endosomal acidification and retrograde transport for the uptake of the highly basic cell-penetrating peptides penetratin, Tat, and oligoarginine was investigated. The effect of a panel of drugs that interfere with discrete steps of endocytosis or Golgi-mediated transport on uptake and cellular distribution of fluorescein-labeled peptide analogues was probed by confocal microscopy, flow cytometry, and fluorescence spectroscopy of whole cell lysates. The analyses were carried out in MC57 fibrosarcoma cells and in HeLa cells. While MC57 fibrosarcoma cells showed some vesicular fluorescence and a pronounced cytoplasmic fluorescence, in HeLa cells little cytoplasmic fluorescence was observed. In MC57 cells the inhibitors of endosomal acidification chloroquine and bafilomycin A1 abolished the release of the peptides into the cytoplasm. Release into the cytosol preserved endosomal integrity. In addition, cellular uptake of the peptides was inhibited by brefeldin A, a compound interfering with trafficking in the transGolgi network. In contrast, nordihydroguaiaretic acid, a drug that stimulates the rapid retrograde movement of both Golgi stacks and trans-Golgi network to the endoplasmic reticulum, promoted a cytoplasmic localization of Tat peptides in peptide-pulsed HeLa cells. The effects of these drugs on trafficking shared characteristics with those reported for the trafficking of plant and bacterial toxins, such as cholera toxin, which reach the cytoplasm by means of retrograde transport. A sequence comparison revealed a common stretch of 8 -10 amino acids with high sequence homology to the Tat peptide. The structural and functional data therefore strongly suggest a common mechanism of import for cationic cell-penetrating peptides and the toxins.

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Cell penetrating PNA constructs regulate galanin receptor levels and modify pain transmission in vivo

Cited by 562 publications

References 28 publications

Cellular delivery of a double-stranded oligonucleotide

Cellular delivery of a double-stranded oligonucleotide

Cell-penetrating and cell-targeting peptides in drug delivery

A Stepwise Dissection of the Intracellular Fate of Cationic Cell-penetrating Peptides

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