Interaction and structure induction of cell-penetrating peptides in the presence of phospholipid vesicles

Magzoub, Mazin; Kilk, Kalle; Eriksson, Lars E.; Langel, Ülo; Gräslund, Astrid

doi:10.1016/s0005-2736(01)00304-2

Cited by 153 publications

(139 citation statements)

References 33 publications

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“…The data indicate that the tryptophan residue may be partially buried among the head groups of the POPG. A similar localization in the head group region of the lipid bilayer has been observed for the CPPs penetratin and transportan (45)(46)(47).…”

Section: Dynorphin Colocalization With Markers Of Subcellular Organelsupporting

confidence: 78%

Translocation of Dynorphin Neuropeptides across the Plasma Membrane

Marinova

Vukojević

Surcheva

et al. 2005

Journal of Biological Chemistry

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Several peptides, including penetratin and Tat, are known to translocate across the plasma membrane. Dynorphin opioid peptides are similar to cell-penetrating peptides in a high content of basic and hydrophobic amino acid residues. We demonstrate that dynorphin A and big dynorphin, consisting of dynorphins A and B, can penetrate into neurons and non-neuronal cells using confocal fluorescence microscopy/immunolabeling. The peptide distribution was characterized by cytoplasmic labeling with minimal signal in the cell nucleus and on the plasma membrane. Translocated peptides were associated with the endoplasmic reticulum but not with the Golgi apparatus or clathrin-coated endocytotic vesicles. Rapid entry of dynorphin A into the cytoplasm of live cells was revealed by fluorescence correlation spectroscopy. The translocation potential of dynorphin A was comparable with that of transportan-10, a prototypical cell-penetrating peptide. A central big dynorphin fragment, which retains all basic amino acids, and dynorphin B did not enter the cells. The latter two peptides interacted with negatively charged phospholipid vesicles similarly to big dynorphin and dynorphin A, suggesting that interactions of these peptides with phospholipids in the plasma membrane are not impaired. Translocation was not mediated via opioid receptors. The potential of dynorphins to penetrate into cells correlates with their ability to induce non-opioid effects in animals. Translocation across the plasma membrane may represent a previously unknown mechanism by which dynorphins can signal information to the cell interior.

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Section: Dynorphin Colocalization With Markers Of Subcellular Organelsupporting

confidence: 78%

Translocation of Dynorphin Neuropeptides across the Plasma Membrane

Marinova

Vukojević

Surcheva

et al. 2005

Journal of Biological Chemistry

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“…As observed with pAntp [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58] , the unconventional internalization of these peptides seems to be neither saturable nor dependent on the cell type 8,10 and could be related to their lipid-binding capacity. 11,12,17,21 As far as the homoarginine peptides are concerned, they have also been described as entering into cells by an energy-dependent nonendocytic process. 34 …”

Section: Other Cell-penetrating Peptidesmentioning

confidence: 99%

Peptide delivery to the brain via adsorptive-mediated endocytosis: Advances with SynB vectors

Drin¹,

Rousselle²,

Scherrmann

et al. 2002

AAPS J

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Biological membranes normally restrict the passage of hydrophilic molecules. This impairs the use of a wide variety of drugs for biomedical applications. To overcome this problem, researchers have developed strategies that involve conjugating the molecule of interest to one of a number of peptide entities that are efficiently transported across the cell membranes. In the past decade, a number of different peptide families with the ability to cross the cell membranes have been identified. Certain of these families enter the cells by a receptor-independent mechanism, are short (10-27 amino acid residues), and can deliver successfully various cargoes across the cell membrane into the cytoplasm or nucleus. Surprisingly, some of these vectors, the SynB vectors, have also shown the ability to deliver hydrophilic molecules across the blood-brain barrier, one of the major obstacles to the development of drugs to combat diseases affecting the CNS.The most important factors determining the extent to which a molecule will be delivered from the blood into the CNS are lipid solubility, molecular mass, and charge. Therefore, based simply on lipid solubility and molecular mass, any peptide-based or oligonucleotide-based neuropharmaceutical will almost certainly be impeded by the BBB. To overcome the limited access of drugs to the brain, at least 3 strategies have been developed that achieve BBB penetration 2-5 :1. Neurosurgery-based strategies, which bypass the BBB by means of intraventricular drug infusion, intracerebral infusion, or disruption of the BBB; 2. Pharmacology-based strategies, some examples of which employ lipidation, or chemical modification of the drug to improve its ability to diffuse across the BBB; and KEYWORDS: intracellular delivery, peptide vector, blood-brain barrier, multidrug resistance. 3. Physiology-based strategies, which take advantage of BBB nutrient carriers or specific receptors, mediating transport via these transporter systems. One example has been to conjugate the therapeutic drug with a protein or a monoclonal antibody that gains access to the brain by either receptor -or adsorptive-mediated transcytosis (eg, transferrin receptor-mediated transfer).2

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“…Until now the mechanism of internalization of TAT peptide is unclear. However a number of evidence show that the internalization does not necessarily involve the presence of a specific cellular receptor or transporter as uptake seems to be temperature and cell type independent [18][19][20][21]. There appears to be two kinds of mechanism involved depending upon the size of the cargo.…”

Section: Introductionmentioning

confidence: 99%

TAT peptide-based micelle system for potential active targeting of anti-cancer agents to acidic solid tumors

Sethuraman

Bae

2007

Journal of Controlled Release

318

205

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A novel drug targeting system for acidic solid tumors has been developed based on ultra pH sensitive polymer and cell penetrating TAT. The delivery system consisted of two components: 1) A polymeric micelle that has a hydrophobic core made of Poly(L-lactic acid) (PLLA) and a hydrophilic shell consisting of Polyethylene Glycol (PEG) conjugated to TAT (TATmicelle), 2) An ultra pH sensitive diblock copolymer of poly(methacryloyl sulfadimethoxine) (PSD) and PEG (PSD-b-PEG). The anionic PSD is complexed with cationic TAT of the micelles to achieve the final carrier, which could systemically shield the micelles and expose them at slightly acidic tumor pH. TATmicelles had particle sizes between 20 to 45 nm and their critical micelle concentrations were 3.5 mg/L to 5.5 mg/ L. The TATmicelles, upon mixing with pH sensitive PSD-b-PEG, showed slight increase in particle size between pH 8.0 and 6.8 (60-90 nm), indicating complexation. As the pH was decreased (pH 6.6 to 6.0) two populations were observed, one that of normal TAT micelles (45 nm) and the other of aggregated hydrophobic PSD-b-PEG. Zeta potential measurements showed similar trend substantiating the shielding/deshielding process. Flowcytometry and confocal microscopy showed significantly higher uptake of TAT micelles at pH 6.6 compared to pH 7.4 indicating shielding at normal pH and deshielding at tumor pH. The flowcytometry indicated that the TAT not only translocates into the cells but is also seen on the surface of the nucleus. These results strongly indicate that the above drug loaded micelles would be able to target any hydrophobic drug near the nucleus.

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Interaction and structure induction of cell-penetrating peptides in the presence of phospholipid vesicles

Cited by 153 publications

References 33 publications

Translocation of Dynorphin Neuropeptides across the Plasma Membrane

Translocation of Dynorphin Neuropeptides across the Plasma Membrane

Peptide delivery to the brain via adsorptive-mediated endocytosis: Advances with SynB vectors

TAT peptide-based micelle system for potential active targeting of anti-cancer agents to acidic solid tumors

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