title: Evaluation of dimerization-inhibitory activities of cyclic peptides containing a β-hairpin loop sequence of the EGF receptor.
abstract: Structure-activity relationships of cyclic peptides mimicking the β-hairpin structure of the 'dimerization arm' at residues 242-259 of the EGF receptor are examined. Cyclic peptides containing the arm head of the β-hairpin loop showed inhibitory activity toward the EGF receptor's dimerization. Cyclic peptides containing a Retro-Inverso sequence of the dimerization arm showed clear inhibitory effects on the dimerization in vitro and efficiently suppressed the proliferation of A431 cells, which abundantly express the EGF receptor on their surface. The effects at a specific hydrophobic site of the loop structure were expected to enhance the interactions with the receptor.
authors.affiliation: Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Mizuguchi
authors.forename: Naho
authors.initials: N
authors.lastname: Ohara
authors.forename: Mika
authors.initials: M
authors.lastname: Iida
authors.forename: Ryunosuke
authors.initials: R
authors.lastname: Ninomiya
authors.forename: Shinji
authors.initials: S
authors.lastname: Wada
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kiso
authors.forename: Kazuki
authors.initials: K
authors.lastname: Saito
authors.forename: Kenichi
authors.initials: K
authors.lastname: Akaji
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation; D055503:Protein Multimerization / Q000187:drug effects*
chemical_list: D010456:Peptides, Cyclic; D066246:ErbB Receptors