Peptide and protein dysfunction are a major aspect for many diseases, but also various peptide based drugs and innovative biomaterials are highly esteemed. Many studies concentrate on peptides due to their versatility, their specificity on the other hand and the complex structural patterns. After cancer, the so called amyloidosis are the second largest research field in the globalized world. The misfolding of functional peptides and proteins is one intrinsic pathologic pattern for many diseases like Alzheimer’s and Parkinson’s disease or diabetes type two. On the other hand uses nature the highly stable and homogenous morphology of amyloids. One famous example is spider silk, but also hormones in the endocrine system are stored in amyloid-like structures. In addition, a range of studies concentrate on applications which are based on functional amyloids. Nevertheless, the collective disadvantages of natural amyloid prone peptides are the difficult isolation and handling. Hence, model peptides with defined design can be used to address certain questions and analytical approaches. In this manuscript presented are two different kinds of amyloid-forming model peptides. The first one is a de novo designed model peptide with a recognition motif for enzymatic phosphorylation. The goal is to understand the impact of the phosphate group and control the phosphorylation process. The second peptide is the critical hydrophobic sequence part of the diabetes type two derived peptide IAPP. With the help of the short peptide sequence, the structure of oligomers during the initial growing phase and the following processes of amyloid formation can be investigated. Thus, insights into so far sparsely examined beginnings of the pathologic event can be described. To transfer the knowledge on model peptides for in vivo studies, a light sensitive caging linker was designed. The optimized synthesis method for the, on natural flavour-based, coumarin linker and the caging process of different model peptides is described in detail. One major problem for peptide applications in vivo is the low bioavailability due to proteolytic digestion. Thus, aim of the fourth project is an idealized protease substrate peptide to study the impact of fluorinated side chains on proteolytic stability. Here presented results are part of a series of comparable studies regarding different kinds of side chain fluorination. Objective is to understand which requirements have to be addressed to inhibit proteolytic digestion of a peptide. As a result, a data bank with this knowledge will be generated as a toolbox for peptide design. One example is the design of metabolic resistant peptide drugs.
