Abstract
Recently, we described a new strategy for the delivery of nucleic acids into mammalian cells, based on an amphipathic peptide of 27residues called MPG, which was designed on the basis of a hydrophobic domain derived from a fusion sequence associated with a nuclearlocalization sequence and separated by a linker. This peptide carrier constitutes a powerful tool for the delivery of nucleic acids in culturedcells, without requiring any covalent coupling. We have examined the conformational states of MPG in its free form and complexed with acargo, as well as its ability to interact with phospholipids, and have investigated the structural consequences of these interactions. In spite ofits similarity to the similarly designed cell-penetrating peptide Pep-1, MPG behaves significantly differently from the conformational point ofview. Circular dichroism (CD) analysis reveals a transition from a nonstructured to ah-sheet conformation upon interaction withphospholipids. We propose that the membrane crossing process involves formation of a transient transmembrane pore-like structure. Partialconformational change of MPG is associated with formation of a complex with its cargo, and an increase in sheet content occurs uponassociation with the cell membrane.