The focus of our research is on the exploration and inhibition of protein-protein interactions based on synthetic mimicry of protein binding sites. The ultimate goal is to modulate protein function through controlled interference with the underlying molecular interactions.
Essentially all biological processes are based on specific binding events, which are initiated by molecular recognition between bio-macromolecules. The design and generation of molecules, which can mimic the binding and/or functional sites of proteins, represents a promising strategy for the exploration an understanding of protein structure and function. In addition to this basic significance, such proteinmimetics are also useful tools for a range of biomedical applications, particularly the development of inhibitors of protein-ligand interactions.
Inhibition of a protein-protein interaction through a binding site mimetic.
We have developed several, stepwise and convergent, solid-phase synthesis strategies for the generation of structurally diverse assembled and scaffolded peptides for the synthetic mimicry of sequentially discontinuous protein binding sites.
Generation of scaffolded peptides as protein binding site mimetics.
Projects
- Development of synthetic (solid-phase synthesis) and biochemical (binding assays) methods for the generation and evaluation of scaffolded and assembled peptides as mimetics of conformationally defined protein bindig sites.
- Design, generation, evaluation of binding affinities and specificities, as well as structural characterisation, of synthetic binding site mimetics of biomedically relevant proteins.
Selected Protein Interactions.
- Cytokine receptor gp130: Interaction with viral interleukin-6
- Protein domains (hYAP-WW, Mena EVH1): Interactions with proline-rich ligands
- Acetylcholine esterase: Interaction with Inhibitor (fasciculin-2)
- Viral surface proteins (HIV-1 gp120, SARS-CoV Spike 1): Interactions with cellular receptors (CD4, chemokine coreceptors, ACE2) SFB 796 (http://www.sfb796.de/)
Synthetic mimetics of the CD4-binding site of HIV gp120 are candidates for virus entry inhibitors, as well as immunogens to elicit virus-neutralizing antibodies.
Funding
Our research is externally funded by the German Federal Ministry of Education and Reserach (BMBF), as well as the German Research Foundation (DFG).