Inhibitory effect of a dimerization-arm-mimetic peptide on EGF receptor activation.
A cyclic decapeptide was chemically synthesized that mimics the loop structure of a beta-hairpin arm of the EGF receptor, which is highly involved in receptor dimerization upon activation by ligand binding. This peptide was revealed to reduce dimer formation of the receptor in a detergent-solubilized extract of epidermoid carcinoma A431 cells and to inhibit receptor autophosphorylation at less than 10 microM in the intact cells.
Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science and 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
Takaaki
T
Mizuguchi
Hiromasa
H
Uchimura
Taeko
T
Kakizawa
Tooru
T
Kimura
Shigeyuki
S
Yokoyama
Yoshiaki
Y
Kiso
Kazuki
K
Saito
D045744:Cell Line, Tumor; D015195:Drug Design; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000737:chemistry*; D006801:Humans; D018716:Molecular Mimicry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D055503:Protein Multimerization / Q000187:drug effects; D013329:Structure-Activity Relationship
D010456:Peptides, Cyclic; D066246:ErbB Receptors