Ribbon‐like Foldamers for Cellular Uptake and Drug Delivery. (22nd September 2017)

• Record Type: Journal Article
• Authors: Vezenkov, Lubomir L.; Martin, Vincent; Bettache, Nadir; Simon, Matthieu; Messerschmitt, Alexandre; Legrand, Baptiste; Bantignies, Jean‐Louis; Subra, Gilles; Maynadier, Marie; Bellet, Virginie; Garcia, Marcel; Martinez, Jean; Amblard, Muriel
• Is Part Of: Chembiochem. Volume 18:Number 21(2017)
• Page Start: 2110
• Page End: 2114
• Publication Date: 2017-09-22
• Subjects: drug delivery -- enzymes -- foldamers -- peptides -- structure–activity relationships; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201700455
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: 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. Abstract : Crossing membranes : Conversion of random coil α‐peptides into short cell‐penetrating foldamers, with controlled periodic distribution of cationic and tryptophan moieties, through a straightforward chemical approach, yields potent cell‐penetrating compounds that are resistant to protease degradation, possess a low content of cationic residues, and are able to deliver bioactive cargo inside the cytoplasm.