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

Work Flow

In our working group expertise can be gained in the following areas:

• Organic synthesis of nonnatural amino acids and other related small molecule building blocks

• Methodology geared toward to improving or redesigning synthetic routes

• Peptide and protein chemistry including solution and solid phase syntheses, as well as ligation techniques to build up the protein backbone, chemoenzymatic approaches, and labelling strategies

• Nanoparticle-peptide conjugates

• Investigations of the properties of novel peptide and proteins by numerous analytical techniques, including but not limited to: circular dichroism spectroscopy; transmission/scanning electron microscopies (including cryo-TEM); fluorescence-based assays; appropriate chromatographic separations; oligomeric state determination by means of light scattering; ultracentrifugation; isothermal titration calorimetry; nuclear magnetic resonance spectroscopy; x-ray crystallography

• Directed evolution approaches based on phage display

• Determination of global changes in conformation in response to different environmental conditions including pH, ionic strength, solvent, metal ions, or the presence of chaperones

• Systematic investigations to determine potential applications for peptide-based drug candidates or materials in biomedicine, biotechnology, and materials science at the nanoscale.