title: The interaction of an antiparasitic peptide active against African sleeping sickness with cell membrane models.
abstract: Zwitterionic peptides with trypanocidal activity are promising lead compounds for the treatment of African Sleeping Sickness, and have motivated research into the design of compounds capable of disrupting the protozoan membrane. In this study, we use the Langmuir monolayer technique to investigate the surface properties of an antiparasitic peptide, namely S-(2,4-dinitrophenyl)glutathione di-2-propyl ester, and its interaction with a model membrane comprising a phospholipid monolayer. The drug formed stable Langmuir monolayers, whose main feature was a phase transition accompanied by a negative surface elasticity. This was attributed to aggregation upon compression due to intermolecular bond associations of the molecules, inferred from surface pressure and surface potential isotherms, Brewster angle microscopy (BAM) images, infrared spectroscopy and dynamic elasticity measurements. 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.
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, 13560-970 São Carlos, SP, Brazil.
authors.forename: Cauê P
authors.initials: CP
authors.lastname: Pascholati
authors.forename: Esteban Parra
authors.initials: EP
authors.lastname: Lopera
authors.forename: Felippe J
authors.initials: FJ
authors.lastname: Pavinatto
authors.forename: Luciano
authors.initials: L
authors.lastname: Caseli
authors.forename: Thatyane M
authors.initials: TM
authors.lastname: Nobre
authors.forename: Maria E D
authors.initials: ME
authors.lastname: Zaniquelli
authors.forename: Tapani
authors.initials: T
authors.lastname: Viitala
authors.forename: Claudius
authors.initials: C
authors.lastname: D'Silva
authors.forename: Osvaldo N
authors.initials: ON
authors.lastname: Oliveira
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry / Q000627:therapeutic use*; D002462:Cell Membrane; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014353:Trypanosomiasis, African / Q000517:prevention & control*
chemical_list: D000981:Antiprotozoal Agents; D010455:Peptides