Castelletto V et al. (2019), Self-Assembly of a Catalytically Active Lipopep...

ECB-ART-48575

ACS Appl Bio Mater 2019 Aug 19;28:3639-3647. doi: 10.1021/acsabm.9b00489.

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

Castelletto V , Edwards-Gayle CJC , Hamley IW , Pelin JNBD , Alves WA , Aguilar AM , Seitsonen J , Ruokolainen J .

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The self-assembly and biocatalytic activity of the proline-functionalized lipopeptide PRW-NH-C16 are examined and compared to that of the related PRW-O-C16 lipopeptide, which differs in having an ester linker between the lipid chain and tripeptide headgroup instead of an amide linker. Lipopeptide PRW-NH-C16 self-assembles into spherical micelles above a critical aggregation concentration, similar to the behavior of PRW-O-C16 reported previously [B. M. Soares et al. Phys. Chem. Chem. Phys., 2017, 19, 1181-1189]. However, PRW-NH-C16 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.

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Genes referenced: pelp1

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References [+] :

Barauskas, Cubic phase nanoparticles (Cubosome): principles for controlling size, structure, and stability. 2005, Pubmed

	Scheme 1. Molecular Structures of PRW-NH-C16 and PRW–O-C16
	Figure 1. Spectroscopic characterization of PRW-NH-C16 self-assembly in water: cac = 0.04 wt % PRW-NH-C16 is determined from the concentration dependence of the emission wavelength of tryptophan (a) and the ANS assay (b); (c) CD spectra below and above the cac, (d) FTIR data above the cac.
	Figure 2. Self-assembly of PRW-NH-C16. (a) Cryo-TEM image showing micelles. (b) SAXS data (open symbols) with a model fit (red line) to the core–shell micelle form factor.
	Figure 3. (a) SAXS profiles for cubosomes made of 10 wt % monoolein + 1 wt % F127 and loaded with (i) 0, (ii) 0.1, (iii) 0.2, and (iv) 0.3 wt % PRW-NH–CH16. (b) Dependence of the spacing of the first reflection in panel a with the concentration of peptide.
	Figure 4. Cryo-TEM images of cubosomes made of 10 wt % monoolein + 1 wt % F127 and loaded with (a–d) 0, (e, f) 0.1, and (g, h) 0.3 wt % PRW-NH-C16. Scale bars are (a, c, g) 100 or (e) 50 nm. Panels b, d, f, and h are FFT images of panels a, c, e, and g, respectively.
	Figure 5. Representative cryo-TEM images of cubosomes made of 10 wt % monoolein + 1 wt % F127 and loaded with (a) 0.1, (b) 0.2, and (c) 0.3 wt % PRWNH-C16. Scale bars are 100 nm. (d) Counting of cubosomes vs vesicles as a function of the PRW-NH-C16 concentration, measured from the corresponding cryo-TEM images.
	Figure 6. Cytotoxicity data, conditions as indicated. Error bars indicate standard deviations of technical errors. (a) 161Br fibroblasts. (b) MCF-7 human breast cancer cells.