Thermally Regulated Reversible Formation of Vesicle-Like Assemblies by Hexaproline Amphiphiles.

Peptides composed of hexaproline and glutamic acid (PE) or lysine (PK) as C-terminal units show thermally promoted aggregation, affording vesicle-like assemblies upon heating to 80 °C. The aggregation is analyzed by dynamic light scattering (DLS), with number-averaged diameters of ca. 600 and 300 nm, respectively, for PE and PK. NMR studies reveal that upon heating the amount of NMR-visible species is reduced to ca. 50% and that an important conformational change is experienced by the molecules in solution. Circular dichroism (CD) shows that at 20 °C the peptides present a polyproline II (PP-II) conformation which is disorganized upon heating. Scanning electron microscopy for samples which were fast frozen at 80 °C reveals vesicle-like assemblies. Using pyrene as a fluorescence probe, a critical aggregation concentration of ca. 30 μM was estimated for PE, while that of PK was above 0.6 mM. The aggregation process is found to be fully reversible and could serve as a basis for development of stimuli responsive carriers.