title: 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.
abstract: 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.
authors.affiliation: Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, 607-8412, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo, 101-0062, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Mizuguchi
authors.affiliation: Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, 607-8412, Japan.
authors.forename: Yasunao
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, 607-8412, Japan.
authors.forename: Naho
authors.initials: N
authors.lastname: Ohara
authors.affiliation: Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, 607-8412, Japan.
authors.forename: Ryunosuke
authors.initials: R
authors.lastname: Ninomiya
authors.affiliation: Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, 607-8412, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Iida
authors.affiliation: Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, 607-8412, Japan.
authors.forename: Honami
authors.initials: H
authors.lastname: Ooe
authors.affiliation: Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, 607-8412, Japan.
authors.forename: Yukako
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, 607-8412, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Takata
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo, 101-0062, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tamamura
authors.affiliation: Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, 607-8412, Japan.
authors.forename: Kenichi
authors.identifier: http://orcid.org/0000-0002-5838-1817
authors.initials: K
authors.lastname: Akaji
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D019281:Dimerization; D066246:ErbB Receptors / Q000737:chemistry*; D006801:Humans; D010455:Peptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D000596:Amino Acids; D010455:Peptides; D010456:Peptides, Cyclic; D066246:ErbB Receptors
keywords: EGF receptor; beta-hairpin loop; cyclic peptide; dimerization; inhibition