Three copies of sequences of peptides of the peptaibol family, known to affect the permeability of the lipid bilayer of membranes, were connected to tris(2-aminoethyl)amine (TREN), a tripodal metal ion ligand, in order to prepare functional peptides capable of modifying the permeability of liposomal membranes. Some of the resulting tripodal polypeptide derivatives are very effective in promoting carboxyfluorescein (CF) leakage from CF-loaded unilamellar vesicles composed of a 70/30 phosphatidylcholine-cholesterol blend. The activity of these novel compounds was shown to be tunable upon metal ion coordination of the TREN subunit, the tripodal apopeptide being far more effective than its ZnII complex. Leakage experiments showed that a minimum number of five aminoacid per peptide chain is required to form active systems. A mechanism is proposed in which the ZnII ion affects the conformation of the template from an extended to a globular one thus acting as an allosteric regulator of the activity of the systems. Molecular modeling studies indicate that when the three peptide chains are connected to the template in the extended conformation, the resulting tripodal polypeptide is able to span the membrane across, thus allowing the formation of permeable channels made of a cluster of molecules. The same change of conformation induces, to some extent, fusion of the membranes of different liposomes.
ZnII as an Allosteric Regulator of Liposomal Membrane Permeability Induced by Synthetic Template-Assembled Tripodal Polypeptides
2002
Abstract
Three copies of sequences of peptides of the peptaibol family, known to affect the permeability of the lipid bilayer of membranes, were connected to tris(2-aminoethyl)amine (TREN), a tripodal metal ion ligand, in order to prepare functional peptides capable of modifying the permeability of liposomal membranes. Some of the resulting tripodal polypeptide derivatives are very effective in promoting carboxyfluorescein (CF) leakage from CF-loaded unilamellar vesicles composed of a 70/30 phosphatidylcholine-cholesterol blend. The activity of these novel compounds was shown to be tunable upon metal ion coordination of the TREN subunit, the tripodal apopeptide being far more effective than its ZnII complex. Leakage experiments showed that a minimum number of five aminoacid per peptide chain is required to form active systems. A mechanism is proposed in which the ZnII ion affects the conformation of the template from an extended to a globular one thus acting as an allosteric regulator of the activity of the systems. Molecular modeling studies indicate that when the three peptide chains are connected to the template in the extended conformation, the resulting tripodal polypeptide is able to span the membrane across, thus allowing the formation of permeable channels made of a cluster of molecules. The same change of conformation induces, to some extent, fusion of the membranes of different liposomes.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
