Antimicrobial nonapeptide leucinostatin A-dependent effects on the physical properties of phospholipid model membranes

The influence exerted by the antimicrobial and antimicotic nonapeptide Leucinostatin A (Leu A) on a biological membrane model made up of dipalmitoylphosphatidylcholine (DPPC) was investigated. Drug-membrane interactions, studied by means of differential scanning calorimetry and Fourier-transform infrared spectroscopy, depend on the behavior of the molecule which positions its hydrophilic part toward the bilayer phospholipid polar heads, while it inserts its hydrophobic portion into the membrane phospholipid acyl chain moiety. Calorimetric experiments showed that the peptide undergoes self-aggregation within the bilayer structure when present at molar fractions higher than 0.03. Peptide-membrane interactions as a function of time were analyzed as well. The latter demonstrated that Leu A inserts rapidly into the outer bilayers of DPPC membranes. Ca-45(2+) uptake by DPPC vesicles gave a reason for the ionophoric activity of Leu A against both mouse thymocytes and artificial membranes, which seems to be correlated to the self-assembling property of the peptide within the bilayers. (C) 2000 Academic Press.