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A Cell‐Penetrating Foldamer with a Bioreducible Linkage for Intracellular Delivery of DNA
Author(s) -
Douat Céline,
Aisenbrey Christopher,
Antunes Stéphanie,
Decossas Marion,
Lambert Olivier,
Bechinger Burkhard,
Kichler Antoine,
Guichard Gilles
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201504884
Subject(s) - foldamer , nucleic acid , chemistry , intracellular , dna , cell penetrating peptide , transfection , histidine , peptide , cell , amphiphile , biophysics , biochemistry , combinatorial chemistry , amino acid , biology , copolymer , gene , organic chemistry , polymer
Despite significant advances in foldamer chemistry, tailored delivery systems based on foldamer architectures, which provide a high level of control over secondary structure, are curiously rare among non‐viral technologies for transporting nucleic acids into cells. A potent pH‐responsive, bioreducible cell‐penetrating foldamer (CPF) was developed through covalent dimerization of a short (8‐mer) amphipathic oligourea sequence bearing histidine‐type units. This CPF exhibits a high capacity to assemble with pDNA and mediates efficient delivery of nucleic acids into the cell. Furthermore, it does not adversely affect cellular viability and was shown to compare favorably with a cognate peptide transfection agent based on His‐rich sequences.