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Foged, C., Franzyk, H., Bahrami, S., Frokjaer, S., Jaroszewski, J. W., Nielsen, H. M., et al. (2008). Cellular uptake and membrane-destabilizing properties of alpha -peptide/beta -peptoid chimeras: lessons for the design of new cell-penetrating peptides. Biochim. Biophys. Acta, Biomembr., 1778(11), 2487–2495.
Abstract: Novel peptidomimetic backbone designs with stability towards proteases are of interest for several pharmaceutical applications including intracellular delivery. The present study concerns the cellular uptake and membrane-destabilizing effects of various cationic chimeras comprised of alternating N-alkylated beta -alanine and alpha -amino acid residues. For comparison, homomeric peptides displaying octacationic functionalities as well as the Tat47-57 sequence were included as ref. compds. Cellular uptake studies with fluorescently labeled compds. showed that guanidinylated chimeras were taken up four times more efficiently than Tat47-57. After internalization, the chimeras were localized primarily in vesicular compartments and diffusively in the cytoplasm. In murine NIH3T3 fibroblasts, the chimeras showed immediate plasma membrane permeabilizing properties, which proved highly dependent on the chimera chain length, and were remarkably different from the effects induced by Tat47-57. Finally, biophys. studies on model membranes showed that the chimeras in general increase the permeability of fluid phase and gel phase phosphatidylcholine (PC) vesicles without affecting membrane acyl chain packing, which suggests that they restrict lateral diffusion of the membrane lipids by interaction with phospholipid head groups. The alpha -peptide/beta -peptoid chimeras described herein exhibit promising cellular uptake properties, and thus represent proteolytically stable alternatives to currently known cell-penetrating peptides.
Keywords: Peptides Role: PRP (Properties), SPN (Synthetic preparation), THU (Therapeutic use), BIOL (Biological study), PREP (Preparation), USES (Uses) (cell-penetrating; alpha -peptide/beta -peptoid chimeras cellular uptake and membrane-destabilizing properties); Biological transport (diffusion; alpha -peptide/beta -peptoid chimeras cellular uptake and membrane-destabilizing properties); Peptides Role: PRP (Properties), SPN (Synthetic preparation), THU (Therapeutic use), BIOL (Biological study), PREP (Preparation), USES (Uses) (fusion peptides, cationic; alpha -peptide/beta -peptoid chimeras cellular uptake and membrane-destabilizing properties); Membrane phase transition (gel-liq. cryst.; alpha -peptide/beta -peptoid chimeras cellular uptake and membrane-destabilizing properties); Biological transport (internalization; alpha -peptide/beta -peptoid chimeras cellular uptake and membrane-destabilizing properties); Biological transport (intracellular; alpha -peptide/beta -peptoid chimeras cellular uptake and membrane-destabilizing properties); Biological transport (permeation; alpha -peptide/beta -peptoid chimeras cellular uptake and membrane-destabilizing properties); Stability (proteolytical; alpha -peptide/beta -peptoid chimeras cellular uptake and membrane-destabilizing properties); Biological transport (uptake; alpha -peptide/beta -peptoid chimeras cellular uptake and membrane-destabilizing properties); Cell membrane; Dissolution; Fibroblast; Human; Melting point; Particle size distribution; Peptidomimetics; Pharmaceutical liposomes; Polydispersity (alpha -peptide/beta -peptoid chimeras cellular uptake and membrane-destabilizing properties); Phosphatidylcholines Role: THU (Therapeutic use), BIOL (Biological study), USES (Uses) (alpha -peptide/beta -peptoid chimeras cellular uptake and membrane-destabilizing properties)
Notes: CAN:150:83542
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ח, י, י, ם, נ, ח, et al. התפסן בשדה השיפון (Vol. מהדורה ש).
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Pettorino, V., Busoni, G., De Simone, A., Morgante, E., Riotto, A., & others,. (2014). Can AMS-02 discriminate the origin of an anti-proton signal? Jcap, 1410(10), 078.
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Busoni, G., De Simone, A., Gramling, J., Morgante, E., & Riotto, A. (2014). On the Validity of the Effective Field Theory for Dark Matter Searches at the LHC, Part II: Complete Analysis for the $s$-channel. Jcap, 1406, 060.
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Okabe, Y., Kusaga, A., Takahashi, T., Mitsumasu, C., Murai, Y., Tanaka, E., et al. (2010). Neural development of methyl-CpG-binding protein 2 null embryonic stem cells: a system for studying Rett syndrome. Brain Res, 1360, 17–27.
Abstract: Mutations in methyl-CpG-binding protein 2 (MeCP2) gene cause the neurodevelopmental disorder Rett syndrome (RTT). Here, we describe a new experimental system that efficiently elucidates the role of MeCP2 in neural development. MeCP2-null and control ES cells were generated by adenoviral conditional targeting and examined for maintenance of the undifferentiated ES cell state, neurogenesis, and gliogenesis during in vitro differentiation. In addition, dopamine release and electrophysiological features of neurons differentiated from these ES cells were examined. Loss of MeCP2 did not affect undifferentiated ES cell colony morphology and growth, or the timing or efficiency of neural stem cell differentiation into Nestin-, TuJ- or TH-positive neurons. In contrast, gliogenesis was drastically accelerated by MeCP2 deficiency. Dopamine production and release in response to a depolarizing stimulus in MeCP2-null ES-derived dopaminergic neurons was intact. However, MeCP2-null differentiated neurons showed significantly smaller voltage-dependent Na(+) currents and A-type K(+) currents, suggesting incomplete maturation. Thus, MeCP2 is not essential for maintenance of the undifferentiated ES cell state, neurogenesis, or dopaminergic function; rather, it is principally involved in inhibiting gliogenesis. Altered neuronal maturity may indirectly result from abnormal glial development and may underlie the pathogenesis of RTT. These data contribute to a better understanding of the developmental roles of MeCP2 and the pathogenesis of RTT.
Keywords: Adenoviridae/genetics; Animals; Blotting, Western; Cell Differentiation/physiology; Cells, Cultured; Chromatography, High Pressure Liquid; Clone Cells; Dopamine/physiology; Electrophysiological Phenomena; Embryonic Stem Cells/*physiology; Genetic Vectors; Glial Fibrillary Acidic Protein/metabolism; Immunohistochemistry; Methyl-CpG-Binding Protein 2/*genetics/*physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Neural Stem Cells/*physiology; Neurogenesis/physiology; Neuroglia/physiology; Neurons/physiology; Rett Syndrome/*genetics/*pathology; Reverse Transcriptase Polymerase Chain Reaction
Notes: PMID:20816763
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