BioDesign Research / 2022 / Article / Tab 2

Review Article

Design of Protein Segments and Peptides for Binding to Protein Targets

Table 2

Examples of application of mutagenesis in design of peptide binders.

Starting pointTargetResults

The structure of the APY hairpin bound to the receptorEphA4 receptorKd as low as 30 nM [47]
C-terminal binding domain of the peptideC5a ReceptorSeries of agonists with a range of ki values as low as 1 μM [48]
Structure of CDK2-cyclinCyclinIC50 values as low as 2.1 0.4 μM [39]
Helix segment from HIV-1 gp41 structuregp41Ki values < 0.2 nM after mutating to new a/B AA [49]
pDI inhibitor discovered through phage display [50], binding motif from p53MDM2/MDMXKD of 0.91 nM for MDM2 and 2.31 nM for MDMX after mutagenesis including ncAAs and crosslinking [51],  nM and  nM against MDM2 and MDMX after adding a res that binds in a newly identified pocket [46]
Helical motif of SARS-COV2 bound to Human ACE-2ACE-2Showed better computational energies for designed binder [44]
Short helical segment from TRF1TRFH-Fbx4G structureubiquitin E3 ligase SCFFbx4kD as low as 23.3 ± 12.8 μM and IC50 of 31.3 μM after mutagenesis [52]