Interactions of amphipathic carrier peptides with membrane components in relation with their ability to deliver therapeutics.
To identify rules for the design of efficient CPPs that can deliver therapeutic agents such as nucleic acids (DNAs, siRNAs) or proteins and PNAs into subcellular compartments, we compared the properties of several primary and secondary amphipathic CPPs. Studies performed with lipid monolayers at the air-water interface have enabled identification of the nature of the lipid-peptide interactions and characterization of the influence of phospholipids on the ability of these peptides to penetrate into lipidic media. Penetration and compression experiments reveal that both peptides interact strongly with phospholipids, and observations on Langmuir-Blodgett transfers indicate that they can modify the lipid organization. Conformational investigations indicate that the lipid-peptide interactions govern the conformational state(s) of the peptides. On the basis of the ability of both peptides to promote ion permeation through both natural and artificial membranes, models illustrating the translocation processes have been proposed. One is based on the formation of a beta-barrel pore-like structure while another is based on the association of helices.
Deshayes
Sébastien
S
CRBM-CNRS, FRE 2593, 34293 Montpellier cedex, France.
Morris
May C
MC
Divita
Gilles
G
Heitz
Frédéric
F
D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism*; D003543:Cysteamine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D003902:Detergents / Q000737:chemistry; D004337:Drug Carriers; D016503:Drug Delivery Systems; D008051:Lipid Bilayers / Q000378:metabolism; D013058:Mass Spectrometry; D008567:Membranes, Artificial; D008954:Models, Biological; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry*; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017550:Spectroscopy, Fourier Transform Infrared
D004268:DNA-Binding Proteins; D003902:Detergents; D004337:Drug Carriers; D008051:Lipid Bilayers; C475074:MPG peptide; D008567:Membranes, Artificial; C503924:Pep-1 peptide; D010455:Peptides; D010743:Phospholipids; D003543:Cysteamine