A focus on the discovery of potent and selective cyclic peptide scaffolds for drug development

In the past, cyclic peptide drugs were commonly discovered by isolation of natural products. However, recent efforts predominantly use high-throughput synthetic or genetically encoded libraries to find potent and selective hits against a range of challenging therapeutic targets. Kawamura et al. (Chem. Sci., 2022, 13, 3256-3262, https://doi.org/10.1039/D1SC06844J) developed a new workflow that can be applied to mRNA display, using high-throughput clustering, SAR investigations and in silico structural studies. This led to the discovery of nanomolar, serum-stable cyclic peptides against the human glucose-dependent insulinotropic peptide receptor (hGIP-R).