Instituto de Física de São Carlos, Universidade de São Paulo, 13560-970 São Carlos, SP, Brazil.
Colloids Surf B Biointerfaces. 2009 Dec 1;74(2):504-10. doi: 10.1016/j.colsurfb.2009.08.018. Epub 2009 Aug 18.
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.
具有杀锥虫活性的两性离子肽是治疗非洲昏睡病的很有前途的先导化合物，并促使人们研究设计能够破坏原生动物膜的化合物。在这项研究中，我们使用 Langmuir 单层技术研究了一种抗寄生虫肽，即 S-（2,4-二硝基苯基）谷胱甘肽二-2-丙酯，及其与包含磷脂单层的模型膜的相互作用。该药物形成稳定的 Langmuir 单层，其主要特征是伴随着负表面弹性的相变。这归因于分子间键合引起的压缩时的聚集，这可以从表面压力和表面电势等温线、Brewster 角显微镜 (BAM) 图像、红外光谱和动态弹性测量中推断出来。当与二棕榈酰磷脂酰胆碱 (DPPC) 共铺展时，即使在高表面压力和低药物用量下，药物也会影响表面压力和单层形态。通过假设药物和 DPPC 分子之间存在排斥、协同相互作用来解释结果。这种排斥相互作用和药物聚集引起的流动性的巨大变化可能与膜的破坏有关，这是寄生虫杀伤特性的关键。
