Fig. 1. ADAPT platform technology. A biomimetic approach for designing β-hairpin peptide inhibitors of PPIs (ADAPTins) based on the plasticity or rigidity of the protein of interest. The relative flexibility of PD1 (bRMSD of 1.68 Å) compared to its ligand PDL1 (bRMSD of 0.76 Å) was calculated from backbone alignments over +400 atoms using unbounded apo-PD1 (PDB: 3RRQ) and apo-PDL1 (PDB: 5C3T) as respective reference. Top panel depicts typical strategies for designing protein epitope mimics into peptide macrocycles or larger protein-derived scaffolds. Bottom panel depicts a novel general approach to mimic CDR-H3s found in antibodies paratopes into ADAPTin scaffolds of varying rigidity. These stand-alone scaffolds (β-strap + β-bulge motifs) can display a broad variety of CDR-H3 loops which can be modified to incorporate electrophilic warheads to covalently bind a protein target.