Evaluation of dimerization-inhibitory activities of cyclic peptides containing a β-hairpin loop sequence of the EGF receptor
Evaluation of dimerization-inhibitory activities of cyclic peptides containing a β-hairpin loop sequence of the EGF receptor
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DOI：
10.1016/j.bmc.2012.08.013
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发表时间：
2012-10-01
影响因子：
3.5
通讯作者：
Akaji, Kenichi
中科院分区：
文献类型：
--
作者：
Mizuguchi, Takaaki;Ohara, Naho;Akaji, Kenichi
研究了模拟EGF受体残基242-259处“二聚臂”的β-发夹结构的环肽的结构-活性关系。含有β-发夹环的臂头的环肽显示出对EGF受体二聚化的抑制活性。含有二聚化臂的反向-反向序列的环肽在体外对二聚化显示出明显的抑制作用，并有效地抑制A431细胞的增殖，A431细胞在其表面上大量表达EGF受体。预期在环结构的特定疏水位点处的作用增强与受体的相互作用。(C)2012爱思唯尔有限公司保留所有权利。
Structure-activity relationships of cyclic peptides mimicking the beta-hairpin structure of the 'dimerization arm' at residues 242-259 of the EGF receptor are examined. Cyclic peptides containing the arm head of the beta-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. (C) 2012 Elsevier Ltd. All rights reserved.