title: Permeation through phospholipid bilayers, skin-cell penetration, plasma stability, and CD spectra of α- and β-oligoproline derivatives.
abstract: After a survey of the special role, which the amino acid proline plays in the chemistry of life, the cell-penetrating properties of polycationic proline-containing peptides are discussed, and the widely unknown discovery by the Giralt group (J. Am. Chem. Soc. 2002, 124, 8876) is acknowledged, according to which fluorescein-labeled tetradecaproline is slowly taken up by rat kidney cells (NRK-49F). Here, we describe details of our previously mentioned (Chem. Biodiversity 2004, 1, 1111) observation that a hexa-β(3)-Pro derivative penetrates fibroblast cells, and we present the results of an extensive investigation of oligo-L- and oligo-D-α-prolines, as well as of oligo-β(2)h- and oligo-β(3)h-prolines without and with fluorescence labels (1-8; Fig. 1). Permeation through protein-free phospholipid bilayers is detected with the nanoFAST biochip technology (Figs. 2-4). This methodology is applied for the first time for quantitative determination of translocation rates of cell-penetrating peptides (CPPs) across lipid bilayers. Cell penetration is observed with mouse (3T3) and human foreskin fibroblasts (HFF; Figs. 5 and 6-8, resp.). The stabilities of oligoprolines in heparin-stabilized human plasma increase with decreasing chain lengths (Figs. 9-11). Time- and solvent-dependent CD spectra of most of the oligoprolines (Figs. 13 and 14) show changes that may be interpreted as arising from aggregation, and broadening of the NMR signals with time confirms this assumption.
authors: Laboratorium für Organische Chemie, Departement Chemie und Angewandte Biowissenschaften, ETH-Zürich, Hönggerberg HCI, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, Switzerland. beata.kolesinska@p.lodz.pl
authors: Beata
authors: B
authors: Kolesinska
authors: Dominika J
authors: DJ
authors: Podwysocka
authors: Magnus A
authors: MA
authors: Rueping
authors: Dieter
authors: D
authors: Seebach
authors: Faustin
authors: F
authors: Kamena
authors: Peter
authors: P
authors: Walde
authors: Markus
authors: M
authors: Sauer
authors: Barbara
authors: B
authors: Windschiegl
authors: Mira
authors: M
authors: Meyer-Ács
authors: Marc
authors: M
authors: Vor der Brüggen
authors: Sebastian
authors: S
authors: Giehring
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000097:blood / Q000737:chemistry* / Q000494:pharmacology; D002942:Circular Dichroism; D019793:Fluorescein / Q000737:chemistry; D006207:Half-Life; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D036103:Nanotechnology; D009842:Oligopeptides / Q000097:blood / Q000737:chemistry* / Q000494:pharmacology; D017433:Protein Structure, Secondary; D051381:Rats; D012997:Solvents / Q000737:chemistry; D013997:Time Factors
chemical_list: D057846:Cell-Penetrating Peptides; D008051:Lipid Bilayers; D009842:Oligopeptides; D012997:Solvents; D019793:Fluorescein