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Effect of Preorganized Charge‐Display on the Cell‐Penetrating Properties of Cationic Peptides
Author(s) -
Nagel Yvonne A.,
Raschle Philipp S.,
Wennemers Helma
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201607649
Subject(s) - cationic polymerization , hela , chemistry , flow cytometry , confocal microscopy , biophysics , cell , glycan , cell membrane , chinese hamster ovary cell , membrane , confocal , cell penetrating peptide , biochemistry , microbiology and biotechnology , glycoprotein , polymer chemistry , biology , receptor , geometry , mathematics
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.