Permeation through Phospholipid Bilayers, Skin-Cell Penetration, Plasma Stability, and CD Spectra of α- and β-Oligoproline Derivatives

Authors

  • Beata Kolesinska,

    Corresponding author
    1. Laboratorium für Organische Chemie, Departement Chemie und Angewandte Biowissenschaften, ETH-Zürich, Hönggerberg HCI, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, (phone: +41-44-632-2990; fax: +41-44-632-1144)
    • Laboratorium für Organische Chemie, Departement Chemie und Angewandte Biowissenschaften, ETH-Zürich, Hönggerberg HCI, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, (phone: +41-44-632-2990; fax: +41-44-632-1144)
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    • Academic guest at ETH Zürich 2011/2012, on leave from the Institute of Organic Chemistry, Technical University of Łodz, Zeromskiego 116, 90-924 Łodz, Poland (phone: +48-42-631-3149).

  • Dominika J. Podwysocka,

    1. Laboratorium für Organische Chemie, Departement Chemie und Angewandte Biowissenschaften, ETH-Zürich, Hönggerberg HCI, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, (phone: +41-44-632-2990; fax: +41-44-632-1144)
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    • Postdoctoral fellow at ETH Zürich 2010/11, financed by Swiss National Science Foundation (No. 200020-117586, 200020-126693).

  • Magnus A. Rueping,

    1. Laboratorium für Organische Chemie, Departement Chemie und Angewandte Biowissenschaften, ETH-Zürich, Hönggerberg HCI, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, (phone: +41-44-632-2990; fax: +41-44-632-1144)
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    • Part of the ETH Dissertation No. 14677, Zürich 2002.

  • Dieter Seebach,

    Corresponding author
    1. Laboratorium für Organische Chemie, Departement Chemie und Angewandte Biowissenschaften, ETH-Zürich, Hönggerberg HCI, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, (phone: +41-44-632-2990; fax: +41-44-632-1144)
    • Laboratorium für Organische Chemie, Departement Chemie und Angewandte Biowissenschaften, ETH-Zürich, Hönggerberg HCI, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, (phone: +41-44-632-2990; fax: +41-44-632-1144)
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  • Faustin Kamena,

    Corresponding author
    1. Max-Planck-Institut für Infektionsbiologie, Charitéplatz 1, D-10117 Berlin, (phone: +49-30-28460-233; fax: +49-30-28460-225)
    • Max-Planck-Institut für Infektionsbiologie, Charitéplatz 1, D-10117 Berlin, (phone: +49-30-28460-233; fax: +49-30-28460-225)
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  • Peter Walde,

    1. Institut für Polymere, Departement Materialwissenschaft, ETH-Zürich, Hönggerberg HCI, Wolfgang-Pauli-Strasse 10, 8093 Zürich, (phone: +41-44-632-0473; fax: +41-44-632-1265)
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  • Markus Sauer,

    1. Physikalisch-Chemisches Institut, Universität Heidelberg, Im Neuenheimer Feld 253, D-69120 Heidelberg
    2. Present address: Lehrstuhl für Biotechnologie & Biophysik, Biozentrum, Julius-Maximilians-Universität Würzburg, D-97074 Würzburg (phone: +49 931-31-88687).
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  • Barbara Windschiegl,

    1. Nanospot GmbH, Johann-Krane-Weg 42, D-48149 Münster, (phone: +49-251-265-38170; fax: +49-251-265-38171)
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  • Mira Meyer-Ács,

    1. Nanospot GmbH, Johann-Krane-Weg 42, D-48149 Münster, (phone: +49-251-265-38170; fax: +49-251-265-38171)
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  • Marc Vor der Brüggen,

    1. Nanospot GmbH, Johann-Krane-Weg 42, D-48149 Münster, (phone: +49-251-265-38170; fax: +49-251-265-38171)
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  • Sebastian Giehring

    Corresponding author
    1. Nanospot GmbH, Johann-Krane-Weg 42, D-48149 Münster, (phone: +49-251-265-38170; fax: +49-251-265-38171)
    • Nanospot GmbH, Johann-Krane-Weg 42, D-48149 Münster, (phone: +49-251-265-38170; fax: +49-251-265-38171)
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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-β3-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-β2h- and oligo-β3h-prolines without and with fluorescence labels (18; Fig. 1). Permeation through protein-free phospholipid bilayers is detected with the nanoFAST biochip technology (Figs. 24). 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 68, resp.). The stabilities of oligoprolines in heparin-stabilized human plasma increase with decreasing chain lengths (Figs. 911). 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.

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