1-palmitoyl-2-oleoylglycero-3-phosphoglycerol and tryptophan-octyl-ester

The orientation and conformation of the cell-penetrating peptide "penetratin" associated with phospholipid vesicle membranes has been determined using polarized-light spectroscopy. The magnitude of orientation of penetratin is unprecedented for a solute in our membrane system, which we believe indicates a strong, specific interaction with the membrane. To validate the spectroscopic technique for studying the orientation of the two tryptophan residues of penetratin, we applied tryptophan octyl ester as a model compound. It is found to be incorporated in the membrane and preferentially oriented with its hydrophobic benzene edge of the indole chromophore pointing into the membrane and its hydrophilic groups oriented toward the water. For penetratin, the results indicate that a central alpha-helical part of the peptide is aligned parallel with the membrane surface, while the ends of the peptide adopt a planar structure. The planes of the two tryptophan side chains show a preferred orientation parallel with the membrane surface, indicating that they are not inserted into the membrane.

Topics: Carrier Proteins; Cell Membrane Permeability; Cell-Penetrating Peptides; Light; Liposomes; Models, Molecular; Phosphatidylcholines; Phosphatidylglycerols; Phospholipids; Protein Conformation; Spectrum Analysis; Tryptophan