Testing the Limits of Peptides and Proteins

Our Research Interests in General

Our research group specializes in the design, synthesis, characterization, and application of peptide model systems to a diverse range of current problems in biomedicine, biotechnology, and materials science. Peptides and proteins have numerous responsibilities in nature. They may be enzymes that perform chemical reactions in cells, structural components of, for example, spider silk, transport molecules, molecular motors, warehouses for the storage of important goods in organisms, not to mention their roles in defense and regulatory processes. Their overwhelming structural and functional diversity depends upon the physical and chemical properties of the amino acid building blocks that they are composed of.

We attempt to systematically evaluate how mutations in the primary structure influence the stability of the diverse quarternary structures formed by α-helices and β-strands. In the former case, the α-helical coiled coil folding motif is studied, and, in the latter case,β-sheet containing amyloid structures are studied. Based on phenomenological rules that govern the behavior of these biologically relevant assemblies, a variety of peptide model systems have been rationally designed. By means of these, we have gained insight into aggregation processes, the complex interactions of nonnatural amino acids in the context of a protein environment, and development strategies for novel chimeric structures using building blocks with alternative backbone connectivities, to give just three examples.

Why Peptide Model Systems?

Peptides are produced in good yields by means of solid phase peptide synthesis (SPPS), and are amenable to analytical techniques such as circular dichroism spectroscopy, tunneling electron microscopy, staining assays with fluorescent dyes, size exclusion chromatography, molar mass determination with the help of light scattering, ultracentrifugation, and nuclear magnetic resonance spectroscopy. Furthermore, they are ideal for a directed evolution approach based on phage display, which we have also established in the group. Due to their small size and amphiphilic nature, they are suitable for determining global changes in conformation in response to different environmental conditions including pH, ionic strength, solvent, metal ions, or the presence of chaperones. Based on systematic investigations made possible by innovative chemical approaches, a variety of applications in biomedicine, biotechnology, and materials science at the nanoscale are currently being pursued.