Fig. 9: Comparison of streptavidin- and chymotrypsin-binding macrocyclic peptide ligands selected using different display technologies.
a Plot of the KD values of unique streptavidin-binding macrocyclic peptide ligands isolated using phage display (blue dots), mRNA display (light grey rhombuses), ribosome display (dark grey hexagons), bacteria display (white triangles), and yeast display (this work, red squares). b Plot depicting the most potent cyclic peptide ligand selected against streptavidin and derived from different literature-reported screening campaigns, which are divided based on selection techniques: yeast display (red square), phage display (blue dots), mRNA display (light grey rhombus), ribosome display (dark grey hexagon), and bacteria display (white triangle). The log10(1/KD) of the most potent cyclic peptide ligand is reported on the y-axis while the square root (log10(size of the naïve library)) is reported on the x-axis. c Plot depicting 7-amino acid ‘one ring’ cyclic peptide ligands selected against streptavidin (PT2) and α-chymotrypsin (PT5). Macrocyclic peptide ligands were isolated by screening either phage-encoded (blue dots) or yeast-encoded (red squares) CX7C naïve libraries of similar size. d Plot of the Ki values of best macrocyclic peptide inhibitors (MP) of α-chymotrypsin isolated using phage display (white triangle) and yeast display (this work, red squares). As reference, the Ki values of the natural eglin c from leech Hirudo medicinalis (70 amino acids; Ki = 0.4 pM)54, the Bowman–Birk inhibitor (BBI) from soybean Glycine max (BBI G.m.; 71 amino acids; Ki = 6 nM)55, the BBI from Torresea cearensis seeds (BBI T.c.; 63 amino acids; Ki = 50 nM)56, the Black-eyed pea trypsin and chymotrypsin inhibitor (BTCI) from Vigna unguiculata (83 amino acids; Ki = 120 nM)57, the natural cyclic peptide chymotrypsin inhibitor HECI from the Asian green frog Hylarana erythraea (17 amino acids, H-TVLRGCWTFSFPPKPCI-NH2; Ki = 3.9 μM)58, the PMP-C inhibitor from insect Locusta migratoria (36 amino acids; Ki = 200 pM)59 and the turkey ovomucoid third domain (OMTKY3; 56 amino acids; Ki = 20 pM)60 are also plotted (blue dots). Data are provided as Source data.
