Action of an Antiparasitic Peptide Active against African Sleeping Sickness in Biomembrane Models

Abstract

Peptides with trypanocidal activity are promising compounds for the treatment of African Sleeping Sickness, which have motivated the research into the ability of these compounds to disrupt the protozoan membrane. In this present study, we used the Langmuir monolayer technique to investigate the surface properties of an antiparasitic and zwitterionic peptide, namely S-(2,4-dinitrophenyl) glutathione di-2-propyl ester, and its interaction with a model membrane comprising a phospholipid monolayer, dipalmitoyl phosphatidyl choline (DPPC). The peptide formed a stable Langmuir monolayer, whose main feature of its surface pressure-area isotherm was the presence of a phase transition accompanied by a negative surface compressional modulus, which was attributed to the aggregation upon compression due to intermolecular bond associations of the molecules. This was inferred from surface pressure and surface potential isotherms, Brewster angle microscopy (BAM) images, Polarization modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS), and dynamic elasticity measurements by the pendant drop technique. When co-spread with dipalmitoyl phosphatidyl choline (DPPC), the drug affected both the surface pressure and the monolayer morphology, even at high surface pressures and with low amounts of the drug. The results were interpreted by assuming a repulsive, cooperative interaction between the drug and DPPC molecules. Such repulsive interaction and the large changes in fluidity arising from drug aggregation may be related to the disruption of the membrane, which is key for the parasite killing property.