title: When cationic cell-penetrating peptides meet hydrocarbons to enhance in-cell cargo delivery.
abstract: Cell-penetrating peptides (CPPs) are short sequences often rich in cationic residues with the remarkable ability to cross cell membranes. In the past 20 years, CPPs have gained wide interest and have found numerous applications in the delivery of bioactive cargoes to the cytosol and even the nucleus of living cells. The covalent or non-covalent addition of hydrocarbon moieties to cationic CPPs alters the hydrophobicity/hydrophilicity balance in their sequence. Such perturbation dramatically influences their interaction with the cell membrane, might induce self-assembling properties and modifies their intracellular trafficking. In particular, the introduction of lipophilic moieties changes the subcellular distribution of CPPs and might result in a dramatically increase of the internalization yield of the co-transported cargoes. Herein, we offer an overview of different aspects of the recent findings concerning the properties of CPPs covalently or non-covalently associated to hydrocarbons. We will focus on the impact of the hydrocarbon moieties on the delivery of various cargoes, either covalently or non-covalently bound to the modified CPPs. We will also provide some key elements to rationalize the influence of the hydrocarbons moieties on the cellular uptake. Furthermore, the recent in vitro and in vivo successful applications of acylated CPPs will be summarized to provide a broad view of the versatility of these modified CPPs as small-molecules and oligonucleotides vectors.
authors: Sorbonne Universités, UPMC Univ Paris 06, UMR 7203, Laboratoire des Biomolécules, Paris, F-75005, France; CNRS, UMR 7203, Laboratoire des Biomolécules, Paris, F-75005, France; Ecole Normale Supérieure (ENS), UMR 7203, Laboratoire des Biomolécules, Département de Chimie, 24 Rue Lhomond, Paris, F-75005, France.
authors: Margherita
authors: M
authors: Di Pisa
authors: Gérard
authors: G
authors: Chassaing
authors: Jean-Marie
authors: JM
authors: Swiecicki
mesh_terms: D000215:Acylation; D002462:Cell Membrane / Q000378:metabolism; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000378:metabolism*; D006838:Hydrocarbons / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008968:Molecular Conformation; D015394:Molecular Structure; D021381:Protein Transport
chemical_list: D057846:Cell-Penetrating Peptides; D006838:Hydrocarbons
keywords: acylated peptide; cell-penetrating peptide; drug delivery; lipopeptide; pyrenebutyrate; targeted drug delivery; transfection; vesicle