Development of inhibitors based on short helical peptides for protein-protein interactions

I explored the effect of α-helical stabilization upon the binding of short peptides to DNAs. When a cross-linked peptide based on the homeodomain of transcription factor was titrated with a target DNA duplex, its dissociation constant (Kd) was calculated to be ca. 0.5 nM. This value was the double-digit smaller than that of the corresponding non-cross-linked peptide. The cross-linked peptide showed high substrate specificity for DNAs at the same level as the original DNA-binding protein.