Abstract
Peptide amphiphiles are class of protein mimics and model systems. Especially, the assembly behavior of peptide amphiphiles has attracted much attention. Not only could the self-assembly behavior provide a starting point for peptide based structures, but the peptide amphiphiles could also be co-assembled with other components in order to introduce additional functionality and/or biocompatibility, leading to a bottom-up fabrication of new nano-materials. Tuning of this self-assembly process should be possible by tuning the hydrophobicity of peptide amphiphiles. This thesis describes the influence of added hydrophobicity, achieved by the introduction of alkyl tails of varying lengths, on peptide (self-) assembly and folding. The influence of additional hydrophobic interactions on a peptide that forms amyloid like fibrils, with the sequence Lys Thr Val Ile Ile Glu, was examined. Specifically the effect of the introduction of an alkyl tail at the N-terminus or C-terminus on the stability of fibrils formed by the peptide is investigated. Furthermore, it was examined whether it is also possible to not only stabilize, but also disassemble these fiber assemblies by manipulating the hydrophobic hydrophilic balance. And the possibility of in situ disassembly of peptide fibrils through the introduction of a cleavable hydrophobic moiety is studied. The influence of introduced hydrophobic interactions on the folding and assembly of a non-self assembling peptide, with the sequence Gly Ala Asn Pro Asn Ala Ala Gly (GANPNAAG), was examined to contrast the effect on hydrophobic interactions of the already fibril forming peptide. These alkyl modified peptides were anchored into liposomes. The effect on folding and anchoring is examined, by varying the length of the alkyl tails on the peptide and liposome composition. Finally, the possibilities were investigated to use alkyl modified peptides, either anchored in liposomes or attached to a carrier protein, for the production of vaccines.
