Discussion

My laboratory is engaged in the discovery and development of peptide macrocycles for therapeutic application. A major focus is the generation of bicyclic peptide ligands of disease targets using a combinatorial approach based on phage display. The bicyclic peptides combine key qualities of antibody therapeutics (high affinity and specificity) and advantages of small molecule drugs (access to chemical synthesis, diffusion into tissue, various administration options). We were able to generate bicyclic peptide antagonists or ligands with nanomolar or even picomolar binding affinity to a range of human disease targets including plasma kallikrein, urokinase-type plasminogen activator, coagulation factor XIIa, matrix metalloproteinase 2 and sortase A. Towards the therapeutic application of the peptides, we have extended their circulation time to several days in mice and we are currently assessing the therapeutic effect of some of the peptides in vivo. An update on recently developed bicyclic peptides and their activities will be presented.