ALAMETHICIN-LIKE BEHAVIOR OF NEW 18-RESIDUE PEPTAIBOLS, TRICHORZINS PA - ROLE OF THE C-TERMINAL AMINO-ALCOHOL IN THE ION-CHANNEL FORMING ACTIVITY

The influences of peptide length, absence of a Glx (Gln/Glu) residue a nd the C-terminal amino alcohol on liposome permeabilization and ion-c hannel characteristics in planar lipid bilayers were examined with two le-residue peptaibols, PA V and PA IX. As compared to the 20-residue alamethicin, both peptides belonging to the newly isolated trichorzin family, lack a proline in the N-terminal part and one of the two Gln/G lu residues in the C-terminal part of the sequence. The two analogues studied here differ among themselves in their C-terminal amino alcohol (tryptophanol for PA V and phenylalaninol for PA IX). These alpha-hel ical peptaibols modify to a similar extent the permeability of liposom es, as measured by leakage of a previously entrapped fluorescent probe . Monitoring tryptophanol fluorescence, a greater embedment of the pep tide PA V is observed in cholesterol-free bilayers. Macroscopic conduc tance studies for PA V and PA IX display alamethicin-like current-volt age curves, with a similar voltage dependence, but a smaller mean numb er of monomers per conducting aggregate is estimated for the tryptopha nol analogue, PA V. Single-channel recordings indicate faster current fluctuations for PA IX, while amplitude histograms show lower conducta nce levels for PA V. Apart from underlining the role of the mismatch b etween helix length and bilayer hydrophobic thickness, these results s tress that the C-terminal tryptophanol favours a stabilization of the conducting aggregates. (C) 1998 Elsevier Science B.V.