IONOPHORIC ACTIVITY OF THE ANTIBIOTIC PEPTAIBOL TRICHORZIN PA-VI - A NA-23-NMR AND CL-35-NMR STUDY

Trichorzin PA VI (Ac Aib(1) Ser Ala Aib Iva Gln Aib Val Aib Gly(10) Le u Aib Pro Leu Aib Aib Gin Pheol(18)) is one of the seven main peptaibo ls forming the natural antibiotic 18-residue peptide mixture biosynthe sised by a Trichoderma harzianum strain. Trichorzins exhibit antimycop lasmic activity resulting from membrane permeability perturbations. Th e membrane permeabilisation process by trichorzin PA VI has been exami ned in egg yolk phosphatidylcholine large unilamellar vesicles (LUV) a nd under conditions of ionic equilibrium by Na-23- and Cl-35-NMR exper iments conducted in the presence of a chemical shift reagent and a rel axation agent, respectively, In such conditions, trichorzin PA VI exch anges both cations and anions across the vesicle bilayers. indicating the absence of ion- and charge-selectivity, in contrast to antibiotic ionophores, such as monensin or nigericin; the Na+ exchange is not inf luenced by the ionic strength, The kinetics of the Na+ exchange have b een found to be third to fourth order with respect to the peptide conc entration, The permeabilisation process of liposomes has been shown to be due to the formation of aggregates of three to four helical peptid e monomers arranged into a supramolecular complex including presumably lipid molecules and forming a badly-defined pore in the bilayer, The major mechanism by which ions may exchange through the bilayer involve s a long-lasting opening of the pores allowing complete exchange of th e internal and external media in an 'all or nothing mode'. (C) 1998 El sevier Science B.V. All rights reserved.