Self-Assembly of a Catalytically Active Lipopeptide and Its Incorporation into Cubosomes

The self-assembly and biocatalytic activity of the proline-functionalized lipopeptide PRW-NH-C 16 are examined and compared to that of the related PRW-O-C 16 lipopeptide, which differs in having an ester linker between the lipid chain and tripeptide headgroup instead of an amide linker. Lipopeptide PRW-NH-C 16 self-assembles into spherical micelles above a critical aggregation concentration, similar to the behavior of PRW-O-C 16 reported previously [B. M. Soares et al. Phys. Chem. Chem. Phys. , 2017, 19, 1181-1189]. However, PRW-NH-C 16 shows an improved catalytic activity in a model aldol reaction. In addition, we explore the incorporation of the biocatalytic lipopeptide into lipid cubosomes. SAXS shows that increasing lipopeptide concentration leads to an expansion of the monoolein cubosome lattice spacing and a loss of long-range cubic order as the lipopeptide is encapsulated in the cubosomes. At higher loadings of lipopeptide, reduced cubosome formation is observed at the expense of vesicle formation. Our results show that the peptide-lipid chain linker does not influence self-assembly but does impart an improved biocatalytic activity. Furthermore, we show that lipopeptides can be incorporated into lipid cubosomes, leading to restructuring into vesicles at high loadings. These findings point the way toward the future development of bioactive lipopeptide assemblies and slow release cubosome-based delivery systems.