TY - JOUR
T1 - The interaction of an antiparasitic peptide active against African Sleeping Sickness with cell membrane models
AU - Pascholati, Cauê P.
AU - Lopera, Esteban Parra
AU - Pavinatto, Felippe J.
AU - Caseli, Luciano
AU - Nobre, Thatyane M.
AU - Zaniquelli, Maria E.D.
AU - Viitala, Tapani
AU - D'Silva, Claudius
AU - Oliveira, Osvaldo N.
N1 - Funding Information:
This work was supported by FAPESP, CNPq and Capes (Brazil).
PY - 2009/12/1
Y1 - 2009/12/1
N2 - 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.
AB - 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.
KW - African Sleeping Sickness
KW - Air-water interface
KW - Drug
KW - Langmuir monolayer
KW - Langmuir-Blodgett film
KW - Peptide
UR - http://www.scopus.com/inward/record.url?scp=70350208804&partnerID=8YFLogxK
U2 - 10.1016/j.colsurfb.2009.08.018
DO - 10.1016/j.colsurfb.2009.08.018
M3 - Article
C2 - 19729286
AN - SCOPUS:70350208804
SN - 0927-7765
VL - 74
SP - 504
EP - 510
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
IS - 2
ER -