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.
Mizuguchi
Takaaki
T
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.
Uchimura
Hiromasa
H
Kakizawa
Taeko
T
Kimura
Tooru
T
Yokoyama
Shigeyuki
S
Kiso
Yoshiaki
Y
Saito
Kazuki
K
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