Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan.
Bioorg Med Chem. 2012 Oct 1;20(19):5730-7. doi: 10.1016/j.bmc.2012.08.013. Epub 2012 Aug 17.
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.
研究了模拟 EGF 受体 242-259 残基“二聚化臂”β-发夹结构的环状肽的结构-活性关系。含有β-发夹环臂头的环状肽对 EGF 受体的二聚化表现出抑制活性。含有二聚化臂的 Retro-Inverso 序列的环状肽在体外对二聚化有明显的抑制作用，并能有效抑制 A431 细胞的增殖，该细胞表面大量表达 EGF 受体。预期环结构特定疏水位点的作用会增强与受体的相互作用。
