Effects of replacement and addition of an amino acid contained in a cyclic peptide corresponding to a β ‐hairpin loop sequence of human EGF receptor

Effects of replacement and addition of an amino acid in a cyclic decapeptide 1 (cyclic‐CYNPTTYQMC) for inhibitory activity to dimerization of human epidermal growth factor receptor (EGFR) were examined. By alanine scanning of 1 corresponding to the arm structure (residues 246–254) of a β ‐hairpin loop sequence (residues 242–259) of EGFR, it was confirmed that replacement of any amino acid in the loop structure lowered the dimerization inhibitory activity of 1 . Among the residues examined, Tyr at position 246 and Thr at 250 were found to be crucial for dimer formation. Addition of an amino acid to the N ‐terminus of 1 also affected the dimerization inhibitory activity. Addition of an amino acid containing a moderately hydrophilic side‐chain increased the inhibitory activity. In contrast, an intramolecular hydrogen bond of 1 is not thought to be crucial for holding the dimer structure on the basis of the dimerization inhibitory activities of N ‐methylated analogues of 1 . These results will be useful for the design and evaluation of a potent dimerization inhibitor as an anti‐proliferation agent. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.