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 hydroph ilic molecules. We have studied three such cell penetrating peptides: pAntp ('penetratin'), pIsl and transportan, pAntp and pIsl originate from the th ird helix of homeodomain proteins (Antennapedia and Isl-1, respectively). T ransportan is a synthetic chimera (galanin and mastoparan). The peptides in the presence of various phospholipid vesicles (neutral and charged) and SD S 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 secon dary structures dominated by random coil. With phospholipid vesicles, neutr al 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 stru cture. We conclude that the exact nature of any secondary structure induced by the membrane model systems is not directly correlated with the common t ransport property of these translocating peptides, (C) 2001 Elsevier Scienc e B,V. All rights reserved.