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Ribbon‐like Foldamers for Cellular Uptake and Drug Delivery
Author(s) -
Vezenkov Lubomir L.,
Martin Vincent,
Bettache Nadir,
Simon Matthieu,
Messerschmitt Alexandre,
Legrand Baptiste,
Bantignies JeanLouis,
Subra Gilles,
Maynadier Marie,
Bellet Virginie,
Garcia Marcel,
Martinez Jean,
Amblard Muriel
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700455
Subject(s) - protease , chemistry , peptidomimetic , peptide , cell penetrating peptide , combinatorial chemistry , intracellular , cationic polymerization , drug delivery , biophysics , biocompatible material , nanotechnology , biochemistry , materials science , enzyme , organic chemistry , biology , medicine , biomedical engineering
Different intracellular delivery systems of bioactive compounds have been developed, including cell‐penetrating peptides. Although usually nontoxic and biocompatible, these vectors share some of the general drawbacks of peptides, notably low bioavailability and susceptibility to protease degradation, that limit their use. Herein, the conversion of short peptide sequences into poly‐α‐amino‐γ‐lactam foldamers that adopt a ribbon‐like structure is investigated. This template is used to distribute critical cationic and/or hydrophobic groups on both sides of the backbone, leading to potent short, cell‐permeable foldamers with a low positive‐charge content. The lead compound showed dramatically improved protease resistance and was able to efficiently deliver a biologically relevant cargo inside cells. This study provided a simple strategy to convert short peptide sequences into efficient protease‐resistant cell‐penetrating foldamers.