Interaction and structure induction of cell-penetrating peptides in the presence of phospholipid vesicles.
Certain short peptides, which are able to translocate across cell membranes with a low lytic activity, can be useful as carriers (vectors) for hydrophilic molecules. We have studied three such cell penetrating peptides: pAntp ('penetratin'), pIsl and transportan. pAntp and pIsl originate from the third helix of homeodomain proteins (Antennapedia and Isl-1, respectively). Transportan is a synthetic chimera (galanin and mastoparan). The peptides in the presence of various phospholipid vesicles (neutral and charged) and SDS micelles have been characterized by spectroscopic methods (fluorescence, EPR and CD). The dynamics of pAntp were monitored using an N-terminal spin label. In aqueous solution, the CD spectra of the three peptides show secondary structures dominated by random coil. With phospholipid vesicles, neutral as well as negatively charged, transportan gives up to 60% alpha-helix. pAntp and pIsl bind significantly only to negatively charged vesicles with an induction of around 60% beta-sheet-like secondary structure. With all three peptides, SDS micelles stabilize a high degree of alpha-helical structure. We conclude that the exact nature of any secondary structure induced by the membrane model systems is not directly correlated with the common transport property of these translocating peptides.
Magzoub
M
M
Department of Biochemistry and Biophysics, Arrhenius Labratories, Stockholm University, Sweden.
Kilk
K
K
Eriksson
L E
LE
Langel
U
U
Gräslund
A
A
D002352:Carrier Proteins / Q000737:chemistry; D057846:Cell-Penetrating Peptides; D002942:Circular Dichroism; D004337:Drug Carriers; D004578:Electron Spin Resonance Spectroscopy; D019004:Galanin / Q000737:chemistry; D036341:Intercellular Signaling Peptides and Proteins; D008081:Liposomes / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D014862:Wasp Venoms / Q000737:chemistry
D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D036341:Intercellular Signaling Peptides and Proteins; D008081:Liposomes; D010446:Peptide Fragments; D010455:Peptides; D010743:Phospholipids; D011993:Recombinant Fusion Proteins; D014862:Wasp Venoms; C110068:transportan; C037500:mastoparan; D019004:Galanin; C414409:penetratin