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Author (up) Foged, C.; Franzyk, H.; Bahrami, S.; Frokjaer, S.; Jaroszewski, J.W.; Nielsen, H.M.; Olsen, C.A. openurl 
  Title Cellular uptake and membrane-destabilizing properties of alpha -peptide/beta -peptoid chimeras: lessons for the design of new cell-penetrating peptides Type Journal Article
  Year 2008 Publication Biochim. Biophys. Acta, Biomembr. Abbreviated Journal  
  Volume 1778 Issue 11 Pages 2487-2495  
  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)  
  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.  
  Address Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Den  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0005-2736 ISBN Medium  
  Area Expedition Conference  
  Notes CAN:150:83542 Approved no  
  Call Number refbase @ admin @ Serial 7356  
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