3D-structure of synthetic peptides and molecular interactions in biomimetic media probed by NMR spectroscopy

Nuclear magnetic resonance (NMR) spectroscopy is a powerful method to characterise the processes of biological macromolecules at an atomic level. The analysis of molecular structure properties enables the specific linkage of a structure with its associated activity. The study of such complex processes motivated the development of today’s biomolecular NMR. Bacteria have developed different strategies to survive in a host. One of these strategies is the continuous translation to advantageous habitats in the host organism. A well-known example is the protein PPEP-1, which initiates translational movement by selectively cleaving proline-proline bonds. So far, it was not known whether the addressed prolineproline bond has to adopt a preferred conformation for effective cleavage. Through detailed NMR spectroscopic investigations, a clearly preferred conformation of the bond could be identified. This finding contributes to a deeper understanding of the survival strategy. Thus, potentially new starting points for treatment options could emerge. The targeted treatment of carcinogenic cells is still of great research interest today. Cellpenetrating peptides could represent a solution for the selective addressing of these, whereby the exact uptake mechanism of the peptides has not yet been sufficiently analysed. In this work, NMR spectroscopic methods were used to show that the interaction between such peptides and membrane mimetics causes the peptide to undergo a conformational change. This represents a further approach in the elucidation of the uptake mechanism of these investigated peptides. Mechanism elucidation is of great importance in the process of protein folding as well. Misfolded proteins are often the cause of various diseases. The refolding of proteins into their functional form is the subject of current research. Small organic molecules can act as folding helpers. The spatial proximity of these molecules to small peptide-derived model systems could be proven with the help of NMR spectroscopy. Thus, in the context of this work, an approach was established with which the site of action of folding helpers on a protein could be localised in the future. Model systems are important in NMR spectroscopy to investigate, among other things,interaction mechanisms of small molecules to macromolecular systems. The investigation of spatial approximations of the interaction partners is one of the essential aspects. The use of micelles is particularly suitable for this purpose. Various molecules were investigated with regard to their positioning in micelles using a variety of NMR spectroscopic methods. The findings of these investigations were then transferred to a postulated reaction mechanism