Peptide mimics of epidermal growth factor (EGF) with antagonistic activity
Peptide mimics of epidermal growth factor (EGF) with antagonistic activity
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DOI：
10.1016/j.jbiotec.2004.10.021
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发表时间：
2005-03-30
影响因子：
4.1
通讯作者：
Kawano, K
中科院分区：
文献类型：
--
作者：
Nakamura, T;Takasugi, H;Kawano, K
表皮生长因子是一种在体内和体外对多种组织细胞有效的生长促进因子。表皮生长因子结合、磷酸化并激活细胞表面的表皮生长因子受体。本研究以抗表皮生长因子单克隆抗体为模板，通过筛选噬菌体展示文库，设计功能肽模拟物。通过使用抗表皮生长因子单克隆抗体作为表皮生长因子结合位点结构的模型，期望高效地探测表皮生长因子的结合位点。从随机肽噬菌体展示文库中，分离与抗表皮生长因子单克隆抗体结合的噬菌体克隆。其中一个噬菌体克隆还表现出与表皮生长因子受体的结合活性。该噬菌体克隆的氨基酸序列与表皮生长因子的一级序列略有相似性。我们将这个基序合成为9个氨基酸的分子内二硫键连接肽。这种合成肽抑制有丝分裂以及表皮生长因子受体酪氨酸磷酸化，这是由表皮生长因子诱导。本研究结果表明，本研究中合成的肽可能模拟表皮生长因子受体结合区的表皮生长因子。(C)2004 Elsevier B.V.保留所有权利。
Epidermal growth factor is a potent growth-promoting factor for a variety of tissue cells in vivo and in vitro. Epidermal growth factor binds, phosphorylates, and activates epidermal growth factor receptors on the cell surface. In this study, we attempted to design functional peptide mimics by panning a phage display library on the anti-epidermal growth factor monoclonal antibody. By using anti-epidermal growth factor monoclonal antibody as a mold of the structure of the binding site of epidermal growth factor, high-efficiency probing was expected. From a random peptide phage display library, phage clones that bind to the anti-epidermal growth factor monoclonal antibody were isolated. One of the phage clones also exhibited binding activity to the epidermal growth factor receptor. The amino acid sequence of this phage clone showed slight similarity to the primary sequence of epidermal growth factor. We synthesized this motif to a 9-amino-acid intramolecularly disulfide-linked peptide. This synthetic peptide inhibited mitogenesis as well as epidermal growth factor receptor tyrosine phosphorylation, which is induced by epidermal growth factor. The present results suggest that the peptide synthesized in this study may mimic the epidermal growth factor receptor-binding region in epidermal growth factor. (C) 2004 Elsevier B.V. All rights reserved.