Design of Protein Segments and Peptides for Binding to Protein Targets

Table 4

Examples of different structural motifs grafted onto existing scaffolds.


Starting point	Target	Scaffolds	Results

Structure of Rev binding to HIV RNAl helical	RRE RNA	-Sheet	Mimicked by a -sheet. K_d as low as 0.1 μM [62]
RGD motif	Integrin	Knottin	Cell binding affinities as low as nM after grafting and affinity maturation [107]
Peptidic antagonist DALK	Bradykinin B₁ receptor	Cyclotide	Functional stable peptides were obtained [110]
RRKRRR epitope that inhibits interaction of VEGF with KDR receptor	VEGF-A	Katalase B1 cyclotide	Maintained biological activity with enhanced serum stability [111]
A number of known melanocortin 4 receptor activating sequences	Melanocortin 4 receptor	Katalase B1 cyclotide	Ki as low as 29 nM after grafting [112]
CVX15 peptide	chemokine receptor 4, CXCR4	MCoTI-I cyclotide	EC₅₀ as low as nM after trying multiple grafting strategies [113]
TCF4 strand bound to -catenin	TCF4/ -catenin interaction	-Hairpin mimic	best μM [116]
Structure of helical motif bound at the interface	botulinum neurotoxin B	Miniprotein of size ~45 residues	K_d as low as 0.5 nM [115]
Structure of helical motif bound at the interface	Influenza haemagglutinin	Miniprotein of size ~45 residues	K_d as low as 5.0 nM [115]
Structure of SARS-CoV2 spike protein with human ACE-2	Human ACE-2	Miniprotein of size 40-65 residues	K_d of ~1 nM after affinity maturation [13]