Formation of transmembrane ionic channels of primary amphipathic cell-penetrating peptides. Consequences on the mechanism of cell penetration.
The ability of three primary amphipathic Cell-Penetrating Peptides (CPPs) CH3-CO-GALFLGFLGAAGSTMGAWSQPKKKRKV-NH-CH2-CH2-SH, CH3-CO-GALFLAFLAAALS LMGLWSQPKKKRKV-NH-CH2-CH2-SH, and CH3-CO-KETWWETWWTEWSQPKKKRKV-NH-CH2-CH2-SH called Pbeta, Palpha and Pep-1, respectively, to promote pore formation is examined both in Xenopus oocytes and artificial planar lipid bilayers. A good correlation between pore formation and their structural properties, especially their conformational versatility, was established. This work shows that the cell-penetrating peptides Pbeta and Pep-1 are able to induce formation of transmembrane pores in artificial bilayers and that these pores are most likely at the basis of their ability to facilitate intracellular delivery of therapeutics. In addition, their behaviour provides some information concerning the positioning of the peptides with respect to the membrane and confirms the role of the membrane potential in the translocation process.
Deshayes
Sébastien
S
CRBM-CNRS, FRE 2593 1919, Route de Mende 34293 Montpellier Cedex, France.
Plénat
Thomas
T
Charnet
Pierre
P
Divita
Gilles
G
Molle
Gérard
G
Heitz
Frédéric
F
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D002468:Cell Physiological Phenomena; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D009865:Oocytes / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D014981:Xenopus
D007473:Ion Channels; D008051:Lipid Bilayers; D010455:Peptides