title: Secondary structure of cell-penetrating peptides controls membrane interaction and insertion.
abstract: The clinical use of efficient therapeutic agents is often limited by the poor permeability of the biological membranes. In order to enhance their cell delivery, short amphipathic peptides called cell-penetrating peptides (CPPs) have been intensively developed for the last two decades. CPPs are based either on protein transduction domains, model peptide or chimeric constructs and have been used to deliver cargoes into cells through either covalent or non-covalent strategies. Although several parameters are simultaneously involved in their internalization mechanism, recent focuses on CPPs suggested that structural properties and interactions with membrane phospholipids could play a major role in the cellular uptake mechanism. In the present work, we report a comparative analysis of the structural plasticity of 10 well-known CPPs as well as their ability to interact with phospholipid membranes. We propose a new classification of CPPs based on their structural properties, affinity for phospholipids and internalization pathways already reported in the literature.
authors.affiliation: Department of Neurochemistry, Stockholm University, S-106 91 Stockholm, Sweden.
authors.forename: Emelía
authors.initials: E
authors.lastname: Eiríksdóttir
authors.forename: Karidia
authors.initials: K
authors.lastname: Konate
authors.forename: Ulo
authors.initials: U
authors.lastname: Langel
authors.forename: Gilles
authors.initials: G
authors.lastname: Divita
authors.forename: Sébastien
authors.initials: S
authors.lastname: Deshayes
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D002463:Cell Membrane Permeability; D016503:Drug Delivery Systems; D006801:Humans; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D010455:Peptides; D010743:Phospholipids