title: Effect of Preorganized Charge-Display on the Cell-Penetrating Properties of Cationic Peptides.
abstract: The effect of preorganized versus undefined charge display on the cellular uptake of cationic cell-penetrating peptides (CPPs) was investigated by comparing conformationally well-defined guanidinylated oligoprolines with flexible oligoarginines. Flow cytometry and confocal microscopy studies with different cancer cell lines (HeLa, MCF-7, and HT-29) showed that preorganization of cationic charges in lateral distances of ≈9 Å enhanced the cellular uptake of CPPs. Binding affinity measurements revealed tighter binding of analogues of cell-surface glycans to the guanidinylated octaproline with localized charges compared to flexible octaarginine, a finding that was further correlated to the cellular uptake by studies with CHO cells deficient in glycans on the outer plasma membrane.
authors.affiliation: Laboratorium für Organische Chemie, ETH Zürich, Vladimir-Prelog-Weg 3, 8093, Zürich, Switzerland.
authors.forename: Yvonne A
authors.initials: YA
authors.lastname: Nagel
authors.affiliation: Laboratorium für Organische Chemie, ETH Zürich, Vladimir-Prelog-Weg 3, 8093, Zürich, Switzerland.
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Raschle
authors.affiliation: Laboratorium für Organische Chemie, ETH Zürich, Vladimir-Prelog-Weg 3, 8093, Zürich, Switzerland.
authors.forename: Helma
authors.identifier: 0000-0002-3075-5741
authors.initials: H
authors.lastname: Wennemers
mesh_terms: D000818:Animals; D016466:CHO Cells; D002412:Cations / Q000737:chemistry / Q000493:pharmacokinetics; D002463:Cell Membrane Permeability; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000493:pharmacokinetics*; D003412:Cricetulus; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics; D011392:Proline / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D055672:Static Electricity
chemical_list: D002412:Cations; D057846:Cell-Penetrating Peptides; D009842:Oligopeptides; C448619:octaarginine; D011392:Proline
keywords: arginine; cellular uptake; heparin; oligoproline; peptides