NUCLEAR MAGNETIC RESONANCE STUDIES OF INTERACTIONS OF PHOSPHOLIPIDS WITH CYCLIC ANTIBIOTICS

The cyclic antibiotics alamethicin, valinomycin and gramicidin S dihydrochloride interact with aqueous dispersions of phospholipids (ox brain phosphatidylserine and egg yolk lecithin). A mixture of each of these antibiotics with the phospholipid dispersed in 0.2 M phosphate buffer (pH 8.0) forms tightly bound phospholipid-antibiotic aggregates, in which the N.M.R. spectrum shows that some sort of cooperative hydrophobic interaction has caused a reduction in the intramolecular motion of the alkyl chains of the phospholipids. In the absence of salt, the interaction of egg yolk lecithin with alamethicin and valinomycin is similar to that observed in phosphate buffer, whereas its interaction with gramicidin S dihydrochloride results in a different type of complex. The resultant particles are smaller and the phospholipid alkyl chains are less tightly bound, resulting in greater molecular motion of the phospholipid compared with egg yolk lecithin/alamethicin (or valinomycin) mixtures. The use of other techniques has shown that the multilamellar structure of the phospholipids is broken down on the addition of each of these antibiotics. These findings may be relevant to the mode of action of some cyclic antibiotics, to the mechanism of induced ion transport across natural membranes observed with many cyclic antibiotics, and also to the question of lipid-protein interactions and membrane organisation in general. © 1969.