Cyclic peptide development builds upon the separate but crucial notions that cyclic peptides can adopt stable bioactive conformations and resist proteolytic degradation, as compared to their linear counterparts. They may also be able offer improved permeability though biological membranes.
The design of cyclic peptides has largely been built around synthetically accessible methods, such as disulphide bond formation, lactam bridges, or peptide-orthogonal click reactions or alkene stapling. In our group we use and optimise these methods, but have also been trying to diversify the cyclic peptide architectures so that optimal ligands for our targets with improved pharmaceutical profiles can be achieved. We find that the investment in synthetic know-how allows us to explore deeper into peptide SAR.
In this presentation, selected examples will be presented that highlight the power of these approaches from anti-infective peptides to ligands for GPCR targets and even peptidomimetic PROTACs.