BioDesign Research / 2022 / Article / Tab 4

Review Article

Design of Protein Segments and Peptides for Binding to Protein Targets

Table 4

Examples of different structural motifs grafted onto existing scaffolds.

Starting pointTargetScaffoldsResults

Structure of Rev binding to HIV RNAl helicalRRE RNA-SheetMimicked by a -sheet. Kd as low as 0.1 μM [62]
RGD motifIntegrinKnottinCell binding affinities as low as  nM after grafting and affinity maturation [107]
Peptidic antagonist DALKBradykinin B1 receptorCyclotideFunctional stable peptides were obtained [110]
RRKRRR epitope that inhibits interaction of VEGF with KDR receptorVEGF-AKatalase B1 cyclotideMaintained biological activity with enhanced serum stability [111]
A number of known melanocortin 4 receptor activating sequencesMelanocortin 4 receptorKatalase B1 cyclotideKi as low as 29 nM after grafting [112]
CVX15 peptidechemokine receptor 4, CXCR4MCoTI-I cyclotideEC50 as low as  nM after trying multiple grafting strategies [113]
TCF4 strand bound to -cateninTCF4/ -catenin interaction-Hairpin mimicbest μM [116]
Structure of helical motif bound at the interfacebotulinum neurotoxin BMiniprotein of size ~45 residuesKd as low as 0.5 nM [115]
Structure of helical motif bound at the interfaceInfluenza haemagglutininMiniprotein of size ~45 residuesKd as low as 5.0 nM [115]
Structure of SARS-CoV2 spike protein with human ACE-2Human ACE-2Miniprotein of size 40-65 residuesKd of ~1 nM after affinity maturation [13]