title: Primary amphipathic cell-penetrating peptides: structural requirements and interactions with model membranes.
abstract: To identify rules for the design of efficient cell-penetrating peptides that deliver therapeutic agents into subcellular compartments, we compared the properties of two closely related primary amphipathic peptides that mainly differ by their conformational state. On the basis of a peptide Pbeta that is nonstructured in water and that promotes efficient cellular uptake of nucleic acids through noncovalent association, we have designed a peptide [Palpha] that is predicted to adopt a helical conformation. We show that [Pbeta] undergoes a lipid-induced conformational transition into a sheet structure, while [Palpha] remains helical. Penetration experiments show that both peptides can spontaneously insert into phospholipid membranes. Analysis of compression isotherms indicates that both peptides interact with phospholipids in the liquid expanded and liquid condensed states. AFM observations reveal that the peptides strongly disrupt the lipid organization of the monolayers and that the conformational state can influence the uptake by model membranes.
authors.affiliation: CRBM, CNRS-FRE 2593, 34293 Montpellier Cedex 5, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Deshayes
authors.forename: Thomas
authors.initials: T
authors.lastname: Plénat
authors.forename: Gudrun
authors.initials: G
authors.lastname: Aldrian-Herrada
authors.forename: Gilles
authors.initials: G
authors.lastname: Divita
authors.forename: Christian
authors.initials: C
authors.lastname: Le Grimellec
authors.forename: Frédéric
authors.initials: F
authors.lastname: Heitz
mesh_terms: D000327:Adsorption; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D008567:Membranes, Artificial; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D008567:Membranes, Artificial; D010455:Peptides